Elsevier

Biological Psychiatry

Volume 62, Issue 5, 1 September 2007, Pages 407-414
Biological Psychiatry

Original Article
Brain Imaging Correlates of Depressive Symptom Severity and Predictors of Symptom Improvement After Antidepressant Treatment

https://doi.org/10.1016/j.biopsych.2006.09.018Get rights and content

Background

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.

Methods

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).

Results

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.

Conclusions

Structural MRI measurements of anterior cingulate cortex could provide a useful predictor of antidepressant treatment response.

Section snippets

Participants

Seventeen participants (mean age ± SD = 44.06 ± 8.36 years; 12 women, 5 men) meeting DSM-IV (American Psychiatric Association 1994) criteria for major depressive disorder according to the Structured Clinical Interview for DSM-IV Axis 1 Disorders (First et al. 1995) were recruited from the general population by local newspaper advertisements. Inclusion criteria were an acute episode of major depressive disorder of the unipolar subtype and a score of at least 18 on the 17-item Hamilton Rating

Depressive Symptom Ratings

Mean baseline symptom score was in the moderate–severe range, HAM-D(0) = 20.9 ± 2.2 (SD), and was reduced by approximately 63% over the course of treatment, HAM-D(8) = 7.8 ± 3.8. The mean rate of normalized symptom change over time, B ≈ −.08, indicates that symptom severity decreased linearly by 8% per week of treatment, with considerable between-subject variability in linear coefficients of symptom change, SD(B) = .025; Figure 1. There was no significant correlation between the coefficient of

Discussion

We have shown that severity of depressive symptoms and response to antidepressant treatment are strongly and independently associated with MRI markers of brain structure and function in people with major depression.

References (46)

  • A. Kugaya et al.

    Brain serotonin transporter availability predicts treatment response to selective serotonin reuptake inhibitors

    Biol Psychiatry

    (2004)
  • H.S. Mayberg et al.

    Deep brain stimulation for treatment-resistant depression

    Neuron

    (2005)
  • P. Muller-Preuss et al.

    Projections from the ’cingular’ vocalization area in the squirrel monkey

    Brain Res

    (1976)
  • M.L. Phillips et al.

    Neurobiology of emotion perception II: Implications for major psychiatric disorders

    Biol Psychiatry

    (2003)
  • D.A. Seminowicz et al.

    Limbic-frontal circuitry in major depression: A path modeling metanalysis

    Neuroimage

    (2004)
  • A. Serretti et al.

    The influence of Serotonin Transporter Promoter Polymorphism (SERTPR) and other polymorphisms of the serotonin pathway on the efficacy of antidepressant treatments

    Prog Neuropsychopharmacol Biol Psychiatry

    (2005)
  • S. Surguladze et al.

    A differential pattern of neural response toward sad versus happy facial expressions in major depressive disorder

    Biol Psychiatry

    (2005)
  • Diagnostic and Statistical Manual of Mental Disorders

    (1994)
  • H. Barbas et al.

    Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression

    BMC Neurosci

    (2003)
  • O. Berton et al.

    New approaches to antidepressant drug discovery: Beyond monoamines

    Nat Rev Neurosci

    (2006)
  • J.D. Bremner et al.

    Positron emission tomography measurement of cerebral metabolic correlates of tryptophan depletion-induced depressive relapse

    Arch Gen Psychiatry

    (1997)
  • T.M. Brody et al.

    Human Pharmacology: Molecular to Clinical

    (1998)
  • E.T. Bullmore et al.

    Methods for diagnosis and treatment of stimulus-correlated motion in generic brain activation studies using fMRI

    Hum Brain Mapp

    (1999)
  • Cited by (0)

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