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2.
Int J Neuropsychopharmacol ; 13(1): 45-59, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19267956

ABSTRACT

It is currently unknown whether the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) depends on specific characteristics of the stimulated frontal area, such as metabolic changes. We investigated the effect of high-frequency rTMS, administered over the most hypometabolic prefrontal area in depressed patients in a two-site, double-blind, randomized placebo-controlled add-on study. Forty-eight patients with medication-resistant major depression underwent magnetic resonance imaging and [(18)F]-fluorodeoxyglucose positron emission tomography (PET) in order to determine a target area for rTMS. After randomization to PET-guided (n = 16), standard (n = 18), or sham rTMS (n = 14) conditions, the patients received 10 sessions of 10-Hz rTMS (1600 pulses/session) at 90% motor threshold. Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores did not differ between PET-guided, standard and sham groups at 2-wk end-point. Exploratory comparison of left PET-guided (n = 9), right PET-guided, standard, and sham rTMS revealed significant effects. The highest improvement in MADRS scores was observed with left PET-guided (60 + or - 31%), significantly superior to sham (30 + or - 37%, p = 0.01) and right-guided (31 + or - 33%, p = 0.02) stimulation. Comparison between left PET-guided and standard rTMS (49 + or - 28%) was not significant (p = 0.12). Comparison between stimulation over dorsolateral prefrontal cortex (BA 9-46), stimulation of other areas, and sham rTMS was statistically significant. Stimulation over BA 9-46 region (n = 15) was superior to sham rTMS (p = 0.02). The results do not support the general hypothesis of increased antidepressant effects of high-frequency rTMS with prefrontal hypometabolism-related PET guidance. Nonetheless, whether metabolism and anatomy characteristics of left frontal area underneath the coil might account for an increase or speeding up of rTMS effects needs further investigation.


Subject(s)
Depressive Disorder, Major/metabolism , Fluorodeoxyglucose F18/metabolism , Prefrontal Cortex/metabolism , Transcranial Magnetic Stimulation/methods , Adult , Antidepressive Agents/therapeutic use , Brain Mapping , Combined Modality Therapy , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/diagnostic imaging , Depressive Disorder, Major/drug therapy , Drug Resistance , Female , Functional Laterality , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Positron-Emission Tomography , Prefrontal Cortex/diagnostic imaging , Transcranial Magnetic Stimulation/psychology , Treatment Outcome
3.
J Psychiatry Neurosci ; 34(2): 127-35, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19270763

ABSTRACT

BACKGROUND: Analysis of cortical folding may provide insight into neurodevelopment deviations, which, in turn, can predispose to depression that responds particularly poorly to medications. We hypothesized that patients with treatment-resistant depression would exhibit measurable alterations in cortical folding. METHODS: We computed hemispheric global sulcal indices (g-SIs) in T(1)-weighted magnetic resonance images obtained from 76 patients and 70 healthy controls. We separately searched for anatomic deviations in patients with bipolar disorder (16 patients with treatment-resistant depression, 25 with euthymia) and unipolar depression (35 patients with treatment-resistant depression). RESULTS: Compared with healthy controls, both groups of patients with treatment-resistant depression exhibited reduced g-SIs: in the right hemisphere among patients with bipolar disorder and in both hemispheres among those with unipolar depression. Patients with euthymic bipolar disorder did not differ significantly from depressed patients or healthy controls. Among patients with bipolar disorder who were taking lithium, we found positive correlations between current lithium dose and g-SIs in both hemispheres. LIMITATIONS: We cannot estimate the extent to which the observed g-SI reductions are linked to treatment resistance and to what extent they are state-dependent. Furthermore, we cannot disentangle the impact of medications from that of the affective disorder. Finally, there is interindividual variation and overlap of g-SIs among patients and healthy controls that need to be considered when interpreting our results. CONCLUSION: Reduced global cortical folding surface appears to be characteristic of patients with treatment-resistant depression, either unipolar or bipolar. In patients with bipolar disorder, treatment with lithium may modify cortical folding surface.


Subject(s)
Bipolar Disorder/pathology , Cerebral Cortex/pathology , Depressive Disorder/pathology , Adult , Antidepressive Agents/therapeutic use , Antimanic Agents/therapeutic use , Bipolar Disorder/drug therapy , Bipolar Disorder/psychology , Depressive Disorder/psychology , Drug Resistance , Electroconvulsive Therapy , Female , Functional Laterality , Humans , Lithium Carbonate/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Psychiatric Status Rating Scales
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