Antidepressant and neurocognitive effects of isoflurane anesthesia versus electroconvulsive therapy in refractory depression.

BACKGROUND:Many patients have serious depression that is nonresponsive to medications, but refuse electroconvulsive therapy (ECT). Early research suggested that isoflurane anesthesia may be an effective alternative to ECT. Subsequent studies altered drug, dose or number of treatments, and failed to replicate this success, halting research on isoflurane's antidepressant effects for a decade. Our aim was to re-examine whether isoflurane has antidepressant effects comparable to ECT, with less adverse effects on cognition. METHOD:Patients with medication-refractory depression received an average of 10 treatments of bifrontal ECT (n = 20) or isoflurane (n = 8) over 3 weeks. Depression severity (Hamilton Rating Scale for Depression-24) and neurocognitive responses (anterograde and retrograde memory, processing speed and verbal fluency) were assessed at Pretreatment, Post all treatments and 4-week Follow-up. RESULTS:Both treatments produced significant reductions in depression scores at Post-treatment and 4-week Follow-up; however, ECT had modestly better antidepressant effect at follow-up in severity-matched patients. Immediately Post-treatment, ECT (but not isoflurane) patients showed declines in memory, fluency, and processing speed. At Follow-up, only autobiographical memory remained below Pretreatment level for ECT patients, but isoflurane patients had greater test-retest neurocognitive score improvement. CONCLUSIONS:Our data reconfirm that isoflurane has an antidepressant effect approaching ECT with less adverse neurocognitive effects, and reinforce the need for a larger clinical trial

Correction: Antidepressant and Neurocognitive Effects of Isoflurane Anesthesia versus Electroconvulsive Therapy in Refractory Depression.

[This corrects the article DOI: 10.1371/journal.pone.0069809.]

Scores on Hamilton Rating Scale for Depression (HRSD-24) at Pretreatment), 24–48 hours after the last treatment (Post-treatment) and at 4-week Follow-up.

<p>Treatment with ECT and ISO result in significant decreases in HRSD-24 depressive symptoms at both Post-treatment and Follow-up compared to Pretreatment. No significant group differences were seen at Post-treatment, but ECT-Matched maintained these low scores better than ISO at Follow-up. <b>+</b> ECT-All vs. ISO p<0.05, <b>&</b> ECT-Matched vs. ISO p<0.05, <b>*</b>Within-group ECT-All Change from Pretreatment p<0.001, <b>#</b> Within-group ECT-Matched Change from Pretreatment p<0.01, <b>@</b> Within-group ISO Change from Pretreatment p<0.005 at Post-treatment and p<0.05 at Follow-up.</p

Scores on the Quick Inventory of Depression Scale (QIDS-SR16) self report form over 21 days of treatment (treatment sessions 1–10).

<p>For brevity, results are depicted showing change over each week, from Day 1 (prior to 1st treatment), Day 7 (prior to 4^th treatment), Day 14 (prior to 7^th treatment), and Day 21 (prior to 10th treatment). <b>*</b>Within-group ECT-All Change from Day 1 p<0.05, <b>#</b> Within-group ECT-Matched Change from Day 1 p<0.05, <b>@</b> Within-group ISO Change from Day 1 p<0.05.</p

Neurocognitive Means (SEM) at Pretreatment, Post-Treatment and Follow-up, Adjusted for Intellectual Level and Age.

<p><i>All p-values are for mean comparisons versus ISO after adjustment for group differences in age and WTAR score. Post-treatment and Follow-up p-values are also adjusted for group differences in Pretreatment and thus test group differences in performance decline or improvement from Pretreatment levels.</i></p><p><i>Cohen's d effect sizes for significant comparisons were consistently large and ranged from 1.1 to 1.7.</i></p

Group Demographics, Intellectual Level, Depression Severity, and Pretreatment Medications.

*<p><i>ECT-All vs. ISO, p<0.05; ECT-Matched vs. ISO nonsignificant.</i></p>**<p><i>ECT-Matched vs. ISO, p<0.05; ECT-All vs. ISO non-significant.</i></p>a<p><i>Group differences non-significant.</i></p>b<p><i>Responders are defined as at least 50% reduction in HRSD score.</i></p>c<p><i>Anticonvulsant medications were stopped during treatment sessions in all groups.</i></p

Tie2 expressing monocytes in the spleen of patients with primary myelofibrosis

Primary myelofibrosis (PMF) is a Philadelphia-negative (Ph-) myeloproliferative disorder, showing abnormal CD34 + progenitor cell trafficking, splenomegaly, marrow fibrosis leading to extensive extramedullary haematopoiesis, and abnormal neoangiogenesis in either the bone marrow or the spleen. Monocytes expressing the angiopoietin-2 receptor (Tie2) have been shown to support abnormal angiogenic processes in solid tumors through a paracrine action that takes place in proximity to the vessels. In this study we investigated the frequency of Tie2 expressing monocytes in the spleen tissue samples of patients with PMF, and healthy subjects (CTRLs), and evaluated their possible role in favouring spleen angiogenesis. We show by confocal microscopy that in the spleen tissue of patients with PMF, but not of CTRLs, the most of the CD14 + cells are Tie2 + and are close to vessels; by flow cytometry, we found that Tie2 expressing monocytes were Tie2 + CD14 low CD16 bright CDL62 - CCR2 - (TEMs) and their frequency was higher (p = 0.008) in spleen tissue-derived mononuclear cells (MNCs) of patients with PMF than in spleen tissue-derived MNCs from CTRLs undergoing splenectomy for abdominal trauma. By in vitro angiogenesis assay we evidenced that conditioned medium of immunomagnetically selected spleen tissue derived CD14 + cells of patients with PMF induced a denser tube like net than that of CTRLs; in addition, CD14 + Tie2 + cells sorted from spleen tissue derived single cell suspension of patients with PMF show a higher expression of genes involved in angiogenesis than that found in CTRLs. Our results document the enrichment of Tie2 + monocytes expressing angiogenic genes in the spleen of patients with PMF, suggesting a role for these cells in starting/maintaining the pathological angiogenesis in this organ