Table_1_Factors associated with antidepressant responses to repetitive transcranial magnetic stimulation in antidepressant-resistant depression.DOCX

BackgroundA significant proportion of patients with major depressive disorder (MDD) failed to respond to antidepressant medications. Repetitive transcranial magnetic stimulation (rTMS) is an effective option for treating such treatment-resistant patients with MDD (TRD). Reliable clinical predictors for antidepressant responses to rTMS remain elusive.MethodsIn total, 212 patients with MDD who failed to respond to at least one adequate antidepressant trial and had a detailed evaluation before rTMS were recruited for chart review. Demographic data, clinical characteristics, psychiatric comorbidities, symptom ratings [e.g., objective and subjective depression, life stress, depression refractoriness by Maudsley Staging Method (MSM)], and antidepressant treatment responses were analyzed.ResultsMSM-subitem1 (duration of current depressive episode; Beta = 0.209, p = 0.004), MSM-subitem5 (a history of ECT treatment; Beta = –0.210, p = 0.004), and psychiatric admissions (Beta = 0.241, p = 0.001) predicted antidepressant response of rTMS treatment. ECT was underutilized (only 3.3%). Psychiatric admissions [Exp(B) = 1.382, p = 0.021], a comorbidity of OCD [0.047, 0.005], and life stress level [0.984, 0.029] predicted the history of ECT treatment.ConclusionSeveral clinical variables (e.g., number of psychiatric admissions, OCD as a comorbidity, and life stress level) were reliable clinical factors associated with antidepressant responses of rTMS treatment and may be utilized in combination with MSM subitems to evaluate levels of TRD.</p

Survival curves of those with major depression or any depressive disorder among women with symptomatic menopausal transition and the control group.

<p>Survival curves of those with major depression or any depressive disorder among women with symptomatic menopausal transition and the control group.</p

Impaired Prefronto-Thalamic Functional Connectivity as a Key Feature of Treatment-Resistant Depression: A Combined MEG, PET and rTMS Study

<div><p>Prefrontal left-right functional imbalance and disrupted prefronto-thalamic circuitry are plausible mechanisms for treatment-resistant depression (TRD). Add-on repetitive transcranial magnetic stimulation (rTMS), effective in treating antidepressant-refractory TRD, was administered to verify the core mechanisms underlying the refractoriness to antidepressants. Thirty TRD patients received a 2-week course of 10-Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). Depression scores were evaluated at baseline (W0), and the ends of weeks 1, 2, and 14 (W14). Responders were defined as those who showed an objective improvement in depression scores ≥50% after rTMS. Left-right frontal alpha asymmetry (FAA) was measured by magnetoencephalography at each time point as a proxy for left-right functional imbalance. Prefronto-thalamic connections at W0 and W14 were assessed by studying couplings between prefrontal alpha waves and thalamic glucose metabolism (PWTMC, reflecting intact thalamo-prefrontal connectivity). A group of healthy control subjects received magnetoencephalography at W0 (N = 50) to study whether FAA could have a diagnostic value for TRD, or received both magnetoencephalography and positron-emission-tomography at W0 (N = 10) to confirm the existence of PWTMC in the depression-free state. We found that FAA changes cannot differentiate between TRD and healthy subjects or between responders and non-responders. No PWTMC were found in the TRD group at W0, whereas restitution of the PWTMC was demonstrated only in the sustained responders at W14 and euthymic healthy controls. In conclusion, we affirmed impaired prefronto-thalamic functional connections, but not frontal functional imbalance, as a core deficit in TRD.</p></div

Distribution of characteristics of women with symptomatic menopausal transition and the control group.

<p>Major depression: 296.2X and 296.3X.</p><p>Any depressive disorder: 296.2X, 296.3X, 300.4, and 311.</p

Medical comorbidity at enrollment and during the whole follow-up period among women with symptomatic menopausal transition (n = 5837) and the control group (n = 23,348).

<p>Medical comorbidity at enrollment and during the whole follow-up period among women with symptomatic menopausal transition (n = 5837) and the control group (n = 23,348).</p

Demographic data and clinical variables between rTMS responders and non-responders.

<p>Note: MDE, major depressive episode; HDRS-17, 17-item Hamilton depression rating scales; BDI, Beck depression index; <b>^#</b> Significant decreases (pair-<i>t</i> test, p<0.05) as compared to baseline values; *p<0.05, **p<0.005.</p

Selection of frontal sensors (all colored squares).

<p>Green: left frontal sensors; Orange: right frontal sensors.</p

Correlations between MEG frontal alpha activity and PET glucose metabolism in healthy controls and in depression before and after successful rTMS treatment.

<p>(A) <i>In healthy subjects</i>. Frontal alpha activity correlated well with glucose metabolism in the thalamus (circled in yellow). (B) <i>Before rTMS.</i> Frontal alpha activity correlated well with glucose metabolism in various parts of the prefrontal cortex, but did not correlate with thalamic activity. (C) <i>After successful rTMS treatment</i>. Frontal alpha activity correlated well with glucose metabolism in the thalamus (circled in yellow), brainstem, precuneus, and cingulate cortices. mPFC, medial prefrontal cortex; dACC, dorsal anterior cingulate cortex; MCC, middle cingulate cortex; SMA, supplementary motor area. Brain regions showing significant negative correlations (cluster-level corrected P<0.001) in each condition are shown in red color.</p

rTMS-related metabolic change in responders (<i>3-month vs. baseline</i>).

<p>Responders demonstrated significantly decreased metabolism in the thalamus, midbrain, cerebellum, posterior cingulate cortex (PCC), basal ganglia, occipital cortex, parahippocampus and subgenual anterior cingulate cortex (sgACC). Contrast bar denotes <i>t</i> values. The significance was set at a cluster-level corrected P<0.001 by paired-<i>t</i> tests.</p

rTMS’s cumulative effects on reversing frontal alpha asymmetry (FAA).

<p>FAA of rTMS responders (in red color) and non-responders (in blue color) showed no difference from baseline (W0) to the end of the 1^st week (W1) and the 2^nd week (W2) after initiation of rTMS. In both groups, rTMS decreased FAA in a dose-dependent manner from W0 to W2, despite lack of statistical significance. During the follow-up period from the end of W2 to the 14^th week (W14), no active rTMS was used, and we observed a gradual rebound of FAA to its baseline value in both groups.</p