Steele JD, Currie J, Lawrie SM, Reid I. Prefrontal cortical functional abnormality in major depressive disorder: a stereotactic meta-analysis. J Affect Disord 101: 1-11

University of Aberdeen, Aberdeen, Scotland, United Kingdom
Journal of Affective Disorders (Impact Factor: 3.38). 09/2007; 101(1-3):1-11. DOI: 10.1016/j.jad.2006.11.009
Source: PubMed


First, the objective was to test the hypothesis that prefrontal cortical regions most often reported to be maximally abnormal in studies of major depressive disorder, correspond to those regions reported maximally active when healthy subjects engage in diverse emotional tasks. Second, the objective was to determine whether such regions are reported typically to be either over or under-active.
Medline and Embase were used to search for neuroimaging studies of major depressive disorder from 1990 to 2005. Forty-two original studies using voxel based techniques were included, and compared with data from our previous meta-analysis on healthy subjects which included one hundred and eighty-one original studies [Steele, J.D., Lawrie, S.M., 2004b. Segregation of cognitive and emotional function in the prefrontal cortex: a stereotactic meta-analysis. Neuroimage 21, 868-875].
The medial prefrontal cortex is the region reported maximally abnormal most often when healthy subjects experience emotion. The region is centred on Broadmans Area (BA) 32 but extends into BA 25. Two further clusters of reported loci were identified in the lateral prefrontal cortex: one in the lateral orbitofrontal region reported active when healthy subjects experience emotion (BA 47); the other centred on a dorsolateral region (BA 46 and 9) associated with cognitive tasks. No reporting bias for overactivity or underactivity was identified.
This study pooled data from diverse studies deliberately. There were insufficient numbers of original studies to support sub-group analyses.
Despite the variability of reports in the literature, activity reported to be abnormal in depressive disorder is particularly localised to those brain regions that represent the substrate for normal emotional experience in healthy subjects.

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    • "The degree of nodes was significantly reduced in the median occipital lobe (including the right cuneus, left calcarine fissure and surrounding cortex), medial temporal lobe (left fusiform gyrus) and prefrontal lobe (including the left orbital inferior frontal gyrus, right median superior frontal gyrus, right orbital middle frontal gyrus, bilateral opercular inferior frontal gyrus and right orbital superior frontal gyrus). Concerns about abnormal changes in the prefrontal lobe of depressed patients have gained momentum[45], especially in the morphology[4647] and functionality[48]. The orbital part mentioned in this study has been previously reported. "
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    ABSTRACT: Depression is closely linked to the morphology and functional abnormalities of multiple brain regions; however, its topological structure throughout the whole brain remains unclear. We collected resting-state functional MRI data from 36 first-onset unmedicated depression patients and 27 healthy controls. The resting-state functional connectivity was constructed using the Automated Anatomical Labeling template with a partial correlation method. The metrics calculation and statistical analysis were performed using complex network theory. The results showed that both depressive patients and healthy controls presented typical small-world attributes. Compared with healthy controls, characteristic path length was significantly shorter in depressive patients, suggesting development toward randomization. Patients with depression showed apparently abnormal node attributes at key areas in cortical-striatal-pallidal-thalamic circuits. In addition, right hippocampus and right thalamus were closely linked with the severity of depression. We selected 270 local attributes as the classification features and their P values were regarded as criteria for statistically significant differences. An artificial neural network algorithm was applied for classification research. The results showed that brain network metrics could be used as an effective feature in machine learning research, which brings about a reasonable application prospect for brain network metrics. The present study also highlighted a significant positive correlation between the importance of the attributes and the intergroup differences; that is, the more significant the differences in node attributes, the stronger their contribution to the classification. Experimental findings indicate that statistical significance is an effective quantitative indicator of the selection of brain network metrics and can assist the clinical diagnosis of depression.
    No preview · Article · Jan 2014 · Neural Regeneration Research
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    • "The clinical heterogeneity in depression is comparably evident from the neurobiological perspective. Over the last 15 years, many studies with increasing sophistication and reviews could narrow down the brain areas presumably involved in the pathophysiology of depression [amygdala, basal ganglia, prefrontal cortex, anterior cingulate cortex (ACC), etc.] but there is still no consensus regarding for instance the hemisphere in which these changes are most prominent or the exact direction of the differences in activation (Drevets, 2000; Davidson et al., 2002; Mayberg, 2003; Fitzgerald et al., 2006; Steele et al., 2007). A comprehensive meta-analysis found only limited overlap between studies exploring brain changes in depression: prefrontal cortex, ACC, insula, and superior temporal gyrus were found to be relatively hypoactive, whereas several limbic, subcortical, and frontal regions showed hyperactivity (Fitzgerald et al., 2008). "
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    ABSTRACT: Objective: The heterogeneity between patients with depression cannot be captured adequately with existing descriptive systems of diagnosis and neurobiological models of depression. Furthermore, considering the highly individual nature of depression, the application of general stimuli in past research efforts may not capture the essence of the disorder. This study aims to identify subtypes of depression by using empirically derived personality syndromes, and to explore neural correlates of the derived personality syndromes. Materials and methods: In the present exploratory study, an individually tailored and psychodynamically based functional magnetic resonance imaging paradigm using dysfunctional relationship patterns was presented to 20 chronically depressed patients. RESULTS from the Shedler-Westen Assessment Procedure (SWAP-200) were analyzed by Q-factor analysis to identify clinically relevant subgroups of depression and related brain activation. Results: The principle component analysis of SWAP-200 items from all 20 patients lead to a two-factor solution: "Depressive Personality" and "Emotional-Hostile-Externalizing Personality." Both factors were used in a whole-brain correlational analysis but only the second factor yielded significant positive correlations in four regions: a large cluster in the right orbitofrontal cortex (OFC), the left ventral striatum, a small cluster in the left temporal pole, and another small cluster in the right middle frontal gyrus. Discussion: The degree to which patients with depression score high on the factor "Emotional-Hostile-Externalizing Personality" correlated with relatively higher activity in three key areas involved in emotion processing, evaluation of reward/punishment, negative cognitions, depressive pathology, and social knowledge (OFC, ventral striatum, temporal pole). RESULTS may contribute to an alternative description of neural correlates of depression showing differential brain activation dependent on the extent of specific personality syndromes in depression.
    Full-text · Article · Dec 2013 · Frontiers in Human Neuroscience
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    • "It has been shown that depressive patients exhibit hypoactivity of the left DLPFC and that activity increases in this region are positively associated with response to treatment (Fitzgerald et al., 2006; Koenigs and Grafman, 2009). Unfortunately, whether left DLPFC perfusion in responders is increased only compared to nonresponders or also compared to healthy volunteers as previously reported (Fitzgerald et al., 2006; Mayberg, 2007; Steele et al., 2007) could not be investigated in this study due to a lack of control group. "
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    ABSTRACT: BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for resistant major depressive disorder. The response rate of rTMS for depression is modest, motivating the search for biomarkers predictive of treatment response. METHODS: Thirteen patients (mean age 45 years, three males) with current major depression resistant to at least one antidepressant trial in the current episode were treated with a 25 day course of rTMS over the left dorsolateral prefrontal cortex (DLPFC). Resting state cerebral perfusion was measured prior to the first day of treatment and after the final day of treatment. Treatment response was measured using the Hamilton Depression Rating Scale - 24 Item (Ham-D). Baseline cerebral perfusion was compared in responders to non-responders. In addition, post-treatment cerebral perfusion was compared to pre-treatment in responders as well as in non-responders. RESULTS: Six individuals responded to rTMS. Responders had greater resting state blood flow in the left DLPFC (the target site) at baseline compared to non-responders. Non-responders showed greater baseline activity in the left medial frontal cortex. Neither group exhibited changes during treatment, nor did the combined group. LIMITATIONS: This study suffers from low sample size and resulting small responder and non-responder subgroups. The sample was not balanced to gender. A normal control group was not included. CONCLUSIONS: We believe this is the first study to compare pre-treatment brain perfusion patterns of depressed individuals who responded to rTMS to those who did not. Our results suggest stronger left DLPFC perfusion in responders and stronger medial prefrontal perfusion in non-responders both at baseline and post-treatment. These results await confirmation in a larger, prospective, placebo-controlled study.
    Full-text · Article · May 2013 · Journal of Affective Disorders
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