Effective connectivity between resting-state networks in depression.

RATIONALE: Although depression has been widely researched, findings characterizing how brain regions influence each other remains scarce, yet this is critical for research on antidepressant treatments and individual responses to particular treatments. OBJECTIVES: To identify pre-treatment resting state effective connectivity (rsEC) patterns in patients with major depressive disorder (MDD) and explore their relationship with treatment response. METHODS: Thirty-four drug-free MDD patients had an MRI scan and were subsequently treated for 6 weeks with an SSRI escitalopram 10 mg daily; the response was defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score. RESULTS: rsEC networks in default mode, central executive, and salience networks were identified for patients with depression. Exploratory analyses indicated higher connectivity strength related to baseline depression severity and response to treatment. CONCLUSIONS: Preliminary analyses revealed widespread dysfunction of rsEC in depression. Functional rsEC may be useful as a predictive tool for antidepressant treatment response. A primary limitation of the current study was the small size; however, the group was carefully chosen, well-characterized, and included only medication-free patients. Further research in large samples of placebo-controlled studies would be required to confirm the results.

Decreased Plasma Levels of Angiotensin-Converting Enzyme Among Patients With Bipolar Disorder.

BACKGROUND: Dysfunctions in the renin-angiotensin system (RAS) seem to be involved in the pathophysiology of several mental illness, including schizophrenia and mood disorders. We carried out a cross-sectional study assessing the levels of RAS-related molecules among bipolar disorder (BD) patients compared to healthy controls. METHODS: our sample consisted of 30 outpatients with BD type 1 (10 males, 20 females, age = 35.53 ± 10.59 years, 14 euthymic, 16 experiencing mood episodes) and 30 healthy controls (10 males, 20 females, age = 34.83 ± 11.49 years). Plasma levels of angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin-II (Ang II), and angiotensin (1-7) [Ang-(1-7)] were determined by ELISA. RESULTS: BD patients experiencing ongoing mood episodes had significantly lower ACE levels compared to controls (median: 459.00 vs. 514.10, p < 0.05). There was no association between the levels of these biomarkers and clinical parameters. CONCLUSION: Our findings support the involvement of RAS dysfunction in the pathophysiology of BD. Considering the potential therapeutic implications linked to a better understanding of the role of RAS dysfunction in BD, studies allowing a better characterization of RAS-related molecules level and activity across different mood states are of high interest.

Revisiting monoamine oxidase inhibitors for the treatment of depressive disorders: A systematic review and network meta-analysis.

BACKGROUND: Monoamine oxidase inhibitors (MAOIs) were the first class of modern antidepressants; however, they are under-utilized as compared to the newer antidepressants. METHODS: In this systematic review, network meta-analysis was used to investigate the comparative efficacy and acceptability of MAOIs for depressive disorders. Overall, the network meta-analysis included 52 double-blind, randomized controlled trials (RCTs) that compared 14 antidepressants or placebo. Across studies, the mean arm size was n = 58 participants from a total N = 6462 (5309 active drug; 1153 placebo). RESULTS: Except fluvoxamine, all antidepressants demonstrated superior efficacy to placebo, and none demonstrated substantially better or worse all-cause dropout rates. Phenelzine demonstrated superior evidence for efficacy compared to all other treatments, and clomipramine demonstrated superior evidence for acceptability compared to all other treatments. LIMITATIONS: The study is primarily limited by low estimate precision due to a relative paucity of studies for some of the included treatment conditions. Further evidence is required to study the relative efficacy of MAOIs against newer antidepressants. CONCLUSIONS: The results of this analysis largely support the re-evaluation of the use of MAOIs as antidepressant agents in the treatment algorithm of depression.