To date, there are no biomarkers for major depressive disorder (MDD) treatment response in clinical use. Such biomarkers could allow for individualized treatment selection, reducing time spent on ineffective treatments and the burden of MDD. In search of such a biomarker, multisite pretreatment and early-treatment (1 week into treatment) structural magnetic resonance (MR) images were acquired from 184 patients with MDD randomized to an 8-week trial of the selective serotonin reuptake inhibitor (SSRI) sertraline or placebo. This study represents a large, multisite, placebo-controlled effort to examine the association between pretreatment differences or early-treatment changes in cortical thickness and treatment-specific outcomes. For standardization, a novel, robust site harmonization procedure was applied to structural measures in a priori regions (rostral and caudal anterior cingulate, lateral orbitofrontal, rostral middle frontal, and hippocampus), chosen based on previously published reports. Pretreatment cortical thickness or volume did not significantly associate with SSRI response. Thickening of the rostral anterior cingulate cortex in the first week of treatment was associated with better 8-week responses to SSRI (p = 0.010). These findings indicate that frontal lobe structural alterations in the first week of treatment may be associated with long-term treatment efficacy. While these associational findings may help to elucidate the specific neural targets of SSRIs, the predictive accuracy of pretreatment or early-treatment structural alterations in classifying treatment remitters from nonremitters was limited to 63.9%. Therefore, in this large sample of adults with MDD, structural MR imaging measures were not found to be clinically translatable biomarkers of treatment response to SSRI or placebo.

This study aimed to identify biomarkers of major depressive disorder (MDD), by relating neuroimage-derived measures to binary (MDD/control), ordinal (severe MDD/mild MDD/control), or continuous (depression severity) outcomes. To address MDD heterogeneity, factors (severity of psychic depression, motivation, anxiety, psychosis, and sleep disturbance) were also used as outcomes. A multisite, multimodal imaging (diffusion MRI [dMRI] and structural MRI [sMRI]) cohort (52 controls and 147 MDD patients) and several modeling techniques-penalized logistic regression, random forest, and support vector machine (SVM)-were used. An additional cohort (25 controls and 83 MDD patients) was used for validation. The optimally performing classifier (SVM) had a 26.0% misclassification rate (binary), 52.2 ± 1.69% accuracy (ordinal) and r = .36 correlation coefficient (p < .001, continuous). Using SVM, R values for prediction of any MDD factors were <10%. Binary classification in the external data set resulted in 87.95% sensitivity and 32.00% specificity. Though observed classification rates are too low for clinical utility, four image-based features contributed to accuracy across all models and analyses-two dMRI-based measures (average fractional anisotropy in the right cuneus and left insula) and two sMRI-based measures (asymmetry in the volume of the pars triangularis and the cerebellum) and may serve as a priori regions for future analyses. The poor accuracy of classification and predictive results found here reflects current equivocal findings and sheds light on challenges of using these modalities for MDD biomarker identification. Further, this study suggests a paradigm (e.g., multiple classifier evaluation with external validation) for future studies to avoid nongeneralizable results.

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Objective Outcomes of concurrent versus staged neck dissection with transoral robotic surgery have not been studied. This study compares outcomes of concurrent versus staged transoral robotic surgery and neck dissection. Design Retrospective administrative database analysis. Setting Article 28 licensed inpatient and outpatient care facilities in New York State. Subjects/Methods Adults undergoing transoral robotic surgery with staged or concurrent neck dissection from 2008 to 2014 were identified in the New York Statewide Planning and Research Collaborative System database. We compared complications, readmissions, subsequent procedures, and length of stay for concurrent versus staged procedures with multivariable logistic regression and multiple linear regression models. Results Of the 425 patients undergoing transoral robotic surgery and neck dissection, 333 had concurrent procedures, and 92 had staged. Risk-adjusted length of stay for concurrent procedures was 42.3% less than that of staged procedures ( P < .0001). Neck dissection timing was not associated with postoperative complications ( P = .41), readmissions ( P = .67), or additional procedures, including reconstruction, tracheostomy, or gastrostomy ( P = .17, .84, .82, respectively). Bleeding (7.8%) was the most common complication, and the majority (78.8%) required reoperation. Bleeding or surgical error was not associated with either concurrent or staged surgery (concurrent vs staged: adjusted odds ratio, 0.68; 95% CI, 0.35-1.37; P = .26). Conclusions Concurrent and staged procedures are equivalent with respect to adverse events, but length of stay is shorter for concurrent procedures. Cost and clinical benefits associated with length of stay are unknown, and it is reasonable to allow operator preference and patient factors to determine surgical logistics.

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In agreement with postmortem studies, we found higher 5-HT autoreceptor binding in MDD selectively in the DRN. 5-HT autoreceptor binding in the combined DRN and MRN is a better biomarker for MDD than in the raphe as a whole.

Serotonin 1A (5-HT ) receptors play a direct role in neuronal development, cell proliferation, and dendritic branching. We hypothesized that variability in 5-HT binding can affect cortical thickness, and may account for a subtype of major depressive disorder (MDD) in which both are altered. To evaluate this, we measured cortical thickness from structural magnetic resonance imaging (MRI) and 5-HT binding by positron emission tomography (PET) in an exploratory study. To examine a range of 5-HT binding and cortical thickness values, we recruited 25 healthy controls and 19 patients with MDD. We hypothesized increased 5-HT binding in the raphe nucleus (RN) would be negatively associated with cortical thickness due to reduced serotonergic transmission. Contrary to our hypothesis, raphe 5-HT binding was positively correlated with cortical thickness in right posterior cingulate cortex (PCC), a region implicated in the default mode network. Cortical thickness was also positively correlated with 5-HT in each cortical region. We further hypothesized that the strength of 5-HT -cortical thickness correlation depends on the number of axons between the raphe nucleus and each region. To explore this we related 5-HT -cortical thickness correlation coefficients to the number of tracts connecting that region and the raphe, as measured by diffusion tensor imaging (DTI) in an independent sample. The 5-HT -cortical thickness association correlated significantly with the number of tracts to each region, supporting our hypothesis. We posit a defect in the raphe may affect the PCC within the default mode network in MDD through serotonergic fibers, resulting in increased ruminative processing.