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Hypofrontality and Negative Symptoms in Major Depressive Disorder

Departments of Psychiatry and Radiology, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, New York

Correspondence: For correspondence or reprints contact: Igor I. Galynker, MD, PhD, 6 Karpas, Beth Israel Medical Center, 1st Ave. at 16th St., New York, NY 10003.

ABSTRACT

The purpose of the current study was to compare regional cerebral blood flow (rCBF) in patients with major depressive disorder (MOD) to that of healthy subjects and to examine the relationship between rCBF, depressive symptoms (DS) and negative symptoms (NS) in these patients. Methods: Eleven psychiatric inpatients with diagnosed (MOD) and 15 normal control subjects were administered the scale for the assessment of negative symptoms (SANS) and the modified Hamilton rating scale for depression with items descriptive of NS excluded (HRSD-DS). Each patient underwent a SPECT scan using ^99mTc-HMPAO at rest. Cortical and subcortical regions of interest (ROIs) were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. Results: Subjects in the MOD group had significantly lower rCBF in the frontal cortex and cinglulate gyrus (MANOVA, p = 0.038) due to differences in dorsolateral prefrontal cortex bilaterally (right F = 7.69, p = 0.01; left F = 8.41, p = 0.01) in the right orbitofrontal cortex (F = 6.79, p = 0.02) and in the cingulate gyrus (F = 5.34, p = 0.03). The MOD group also had lower rCBF in the posterior cortical structures (MANOVA, p = 0.072), which was due to decreased perfusion in the right parietal cortex (F = 7.54, p = 0.01). There were negative correlations between the SANS total score and rCBF in both the left dorsolateral prefrontal cortex (Pearson's correlation coefficient r =.–67, p < 0.05) and the left anterior temporal cortex (r = –0.71, p < 0.01) in MOD patients. Additionally, there were positive correlations between HRSD scores and rCBF in the left anterior temporal (r = 0.71, p < 0.01), left dorsolateral prefrontal (r = 0.70, p < 0.01), right frontal (r = 0.82, p < 0.01) and right posterior temporal (r = 0.74, p < 0.01) cortices. Cerebral blood flow was not correlated with either mini-mental state examination scores or age. Conclusion: This preliminary study replicates the finding of hypofrontality in MOD and indicates that decreased perfusion is associated specifically with negative symptom severity. These results support the hypothesis that, in MOD, negative symptoms and symptoms of depression are distinct phenomena and underscore the importance of negative symptom evaluation in neuroimaging studies of MOD and other disorders.

Key Words: technetium-99m-HMPAO SPECT • regional cerebral blood flow • depression • negative symptoms • dorsolateral prefrontal cortex • temporal cortex

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