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Purpose: Existing literature describes the interdependence between neurotrophic and vascular signals in the central nervous system. We hypothesize a similar crosstalk important to extremity healing involving the peripheral nervous system and angiogenic cells. Nerves are difficult to capture via axons found in the periphery alone. Thus, we have interrogated from publicly available single-nuclei transcriptomic data of peripheral nerve soma (dorsal root ganglia), injured by physical transection or chemically induced pain. We present a combined analysis of extremity polytrauma (burn/tenotomy HO model) and peripheral nerve (post-injury/pain DRG model) to determine if there is expression of vascular signals by nerves and reciprocal neurotrophic signals by cells local to the injury site. Methods: A 30% dorsal burn and Achilles transection was performed in C57/BL6J mice. The tendon site tissues were harvested from baseline (t0) and day 7, 42 after induction. Samples were prepared for library generation on a 10x Genomics Chromium Controller, sequenced on a Illumina HiSeq 4000, and analyzed with Cell Ranger Software for pre-processing and alignment to the mm10 genome. DRG analyses and clusters were abstracted from NIH-GEO (GSE154659). Downstream analyses including unsupervised clustering downstream analyses were performed with Seurat. Results: We first examined candidate neurotrophins and vascular signals in nerve (DRG), finding robust upregulation of Bdnf and Vegfa. In HO, the site of injury contains many cells that may potentially respond to these signals. Indeed, in sequencing data from the pre-HO anlagen, endothelium and smooth muscle cell populations express upregulation for receptors to the nerve-derived Vegfa via Flt1/VEGFR1. This population in addition to being sensitive to the VEGFA ligand, also demonstrates upregulation of Ngf, signifying a potential vasculo-neuro axis where a vascular signal induces endothelium/SMCs to produce neurotrophic signals. Completing the circuit, the original DRG cells and by logical extension, regenerating peripheral nerves, are highly enriched for the neurotrophin receptors: Ntrk1/TrkA (responsive to the SMC derived NGF), Ntrk2/TrkB (responsive to the nerve-autonomous BDNF), and Ntrk3/TrkC (partial combined NGF/BDNF response). This potentially signifies a feedforward loop where peripheral nerve induces angiogenesis which in return, promotes nascent nerve ingrowth in a cyclical process. Indeed, in targeted knockout of a local VEGFA source (VegfaPrrx1 mice), the injury site demonstrates parallel reduction in vascular density (77%) and reduction in nerve fiber frequency (62%) within the HO site. Conclusions: These findings represent the first work characterizing the coordination between neurogenic and angiogenic transcription programs following extremity trauma. We demonstrate through NextGen sequencing, evidence of neuroangiogenic crosstalk following musculoskeletal/neural injury. This VEGFA/NGF axis involves vascular signaling as a potential source for additional proliferation of NGF expressing pericyte/SMCs. The presented data describe the potential nerve-driven regulation contributing to the formation of HO at the extremity that with antagonism or inhibition may lead to better treatments for aberrant extremity wound healing.

Purpose: It is controversial whether subsidence after trapeziectomy prognosticates pain, poor outcomes, and need for revision. The aim of this study was to investigate the degree of subsidence following trapeziectomy and whether subsidence contributes to poor outcomes. Methods: An IRB approved retrospective review of all patients who underwent trapeziectomy for osteoarthritis of the first carpometacarpal (CMC) joint was conducted from 2003 to 2019. Patients with available radiographic imaging greater than three months postoperatively were included. Patients with arthritis of the metacarpophalangeal joint of the thumb, arthritis of radiocarpal, distal radioulnar, and midcarpal joints were excluded. Demographic information, pain scores, and revision procedures were recorded. Conolly-Rath patient function scores were determined. Subsidence was measured by the ratio of the difference between the trapezial space (TS = distance from base of thumb metacarpal to scaphoid) preoperatively and TS postoperatively over the TS preoperatively. Patients were divided as having a high degree of subsidence (≥50%) or low degree of subsidence (

Objective: The authors hypothesized that the depression treatment preferences of elderly home care patients would vary by their experience of depression and that preferences for active treatment would be associated with current depression and with antidepressant treatment.Methods: The authors conducted cross-sectional secondary analyses of data from the TRIAD study (Training in the Assessment of Depression) of 256 randomly selected elderly patients newly admitted to home care. The study assessed preference for active treatments (medication or psychotherapy) and nonactive or complementary approaches (such as religious activities or doing nothing). Nondepressed patients were asked to choose as if they had serious depression. Two separate indicators of depression experience were used: a current diagnosis of major or minor depression and current or previous antidepressant treatment.Results: Of the 256 patients, 16% (N=41) met criteria for major or minor depression. Forty-seven percent of the sample (N=121) preferred an active treatment as their first choice, and others preferred nonactive or complementary approaches. Logistic regression indicated that current antidepressant use, previous psychotherapy experience, white or Hispanic race-ethnicity (versus black), greater impairment in instrumental activities of daily living, and less personal stigma about depression were independently associated with preference for an active treatment.Conclusions: Elderly home care patients had a variety of treatment preferences, ranging from active treatments, to religious or spiritual activities, to no treatment. Several factors were associated with a preference for active treatment, including treatment experience, physical impairment, race-ethnicity, and attitudes and beliefs. An understanding of patient preferences may help engage older depressed home care patients in treatment. [ABSTRACT FROM AUTHOR]

Major depressive disorder with psychotic features (psychotic depression) is a severe disorder. Compared with other psychotic disorders such as schizophrenia, relatively few studies on the neurobiology of psychotic depression have been pursued. Neuroimaging studies investigating psychotic depression have provided evidence for distributed structural brain abnormalities implicating the insular cortex and limbic system. We examined structural brain networks in participants (N = 245) using magnetic resonance imaging. This sample included healthy controls (n = 159) and the largest cross-sectional sample of patients with remitted psychotic depression (n = 86) collected to date. All patients participated in the Study of Pharmacotherapy of Psychotic Depression II randomized controlled trial. We used a novel, whole-brain, data-driven parcellation technique-non-negative matrix factorization-and applied it to cortical thickness data to derive structural covariance networks. We compared patients with remitted psychotic depression to healthy controls and found that patients had significantly thinner cortex in five structural covariance networks (insular-limbic, occipito-temporal, temporal, parahippocampal-limbic, and inferior fronto-temporal), confirming our hypothesis that affected brain networks would incorporate cortico-limbic regions. We also found that cross-sectional depression and severity scores at the time of scanning were associated with the insular-limbic network. Furthermore, the insular-limbic network predicted future severity scores that were collected at the time of recurrence of psychotic depression or sustained remission. Overall, decreased cortical thickness was found in five structural brain networks in patients with remitted psychotic depression and brain-behavior relationships were observed, particularly between the insular-limbic network and illness severity.

Background: There is paucity of neurobiological knowledge about major depressive disorder with psychotic features ("psychotic depression"). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls., Methods: We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls., Findings: The Toronto sample included 28 patients (mean [SD], age 56·2 [13·7]) and 39 controls (age 55·1 [13·5]). The Replication sample included 29 patients (age 56·1 [17·7]) and 36 controls (age 48·3 [17·9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t = 4·831; p = 0·001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t = 4·144; p = 0·003, FWE corrected)., Interpretation: Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories., Funding: National Institute of Mental Health., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Psychotic depression (PD) is a severe disabling disorder with considerable morbidity and mortality. Electroconvulsive therapy and pharmacotherapy are each efficacious in the treatment of PD. Expert guidelines recommend the combination of antidepressant and antipsychotic medications in the acute pharmacologic treatment of PD. However, little is known about the continuation treatment of PD. Of particular concern, it is not known whether antipsychotic medication needs to be continued once an episode of PD responds to pharmacotherapy. This issue has profound clinical importance. On the one hand, the unnecessary continuation of antipsychotic medication exposes a patient to adverse effects, such as weight gain and metabolic disturbance. On the other hand, premature discontinuation of antipsychotic medication has the potential risk of early relapse of a severe disorder., Methods/design: The primary goal of this multicenter randomized placebo-controlled trial is to assess the risks and benefits of continuing antipsychotic medication in persons with PD once the episode of depression has responded to treatment with an antidepressant and an antipsychotic. Secondary goals are to examine age and genetic polymorphisms as predictors or moderators of treatment variability, potentially leading to more personalized treatment of PD. Individuals aged 18-85 years with unipolar psychotic depression receive up to 12 weeks of open-label treatment with sertraline and olanzapine. Participants who achieve remission of psychosis and remission/near-remission of depressive symptoms continue with 8 weeks of open-label treatment to ensure stability of remission. Participants with stability of remission are then randomized to 36 weeks of double-blind treatment with either sertraline and olanzapine or sertraline and placebo. Relapse is the primary outcome. Metabolic changes are a secondary outcome., Discussion: This trial will provide clinicians with much-needed evidence to guide the continuation and maintenance treatment of one of the most disabling and lethal of psychiatric disorders.

Objective: This study examined the rate and predictors of major depression six months after outpatient mental health admission., Methods: Assessments were conducted at admission and three and six months later among 166 participants. Antidepressant treatment adequacy and depression outcomes were assessed at follow-ups., Results: Predictors of major depression at six months included nonremission status at three months (odds ratio [OR]=3.56, p=.003), inadequacy of early pharmacotherapy (OR=2.73, p=.009), worse physical functioning measured by the 36-Item Short-Form Health Survey (OR=.975, p<.001), and being unmarried (OR=2.54, p=.031)., Conclusions: The findings support the effects of baseline physical disability, marital status, early treatment adequacy, and early remission on the course of major depression. The identification of individuals who do not receive intensive pharmacotherapy or who have not recovered by three months may provide opportunities for interventions to optimize six-month outcomes and to prevent the development of a persistent depression.

Assess patients with major depression or substance abuse for suicide ideation, as they are at elevated risk for self-harm. Severity of suicide ideation is associated with suicide risk. Its assessment, therefore, should proceed sequentially from passive to active suicide ideation, to a specific detailed plan, including intention to harm oneself, reasons for living, and impulse control. Primary care patients at mild to moderate risk for suicide can be effectively treated in primary care settings; however, patients at high risk should be referred to mental health specialists given their need for intensive treatments and frequent monitoring.

Objective: This article describes the development, administration, and reliability of the Cornell Services Index (CSI), a new instrument that measures health service use. The CSI was developed to create a standardized measure of the quantity and characteristics (for example, site and provider) of services used by adults. Descriptive data are provided to illustrate the application of the CSI in a community sample of adults who were newly admitted to outpatient mental health clinics. These data provide information about the pathways to care., Methods: The interrater and test-retest reliability of the CSI were evaluated by using a sample of 40 adults who were seeking mental health treatment. Descriptive data on service use in a sample of 1,279 adults seeking care in outpatient mental health clinics was provided to demonstrate the application of the CSI., Results: The CSI is a portable, easy to use, and brief assessment of service use. It has good interrater and test-retest reliability among adults without cognitive impairment. In the three months before seeking care, 31 percent of the adults interviewed had made a mental health visit, 36 percent had been hospitalized, and more than half (59 percent) had made a medical visit. Twenty-three percent of adults had sought care from a hospital's emergency department., Conclusions: The CSI is a reliable method to assess health service use for adults. The measure can extend assessment of use beyond the traditional mental health service use questions and provide a snapshot of service use patterns across types, providers, and sites of service among adults who seek mental health care.

This review centers on the development of diagnostic criteria for depression of Alzheimer's disease. It describes: risk-factors and neurobiological correlates, epidemiology, clinical characteristics and course, assessment, treatment, economics, a description of the criteria and future research directions. Overall, there is substantial evidence for depression of Alzheimer's disease. Further research is needed to better define core symptoms, clinical course and efficacy of treatments.

Objective: Major depression is undertreated despite the availability of effective treatments. Psychological barriers to treatment, such as perceived stigma and minimization of the need for care, may be important obstacles to adherence to the pharmacologic treatment of major depression. The authors examined the impact of barriers that were present at the initiation of antidepressant drug therapy on medication adherence in a mixed-age sample of outpatients with major depression., Methods: A two-stage sampling design was used to identify adults with a diagnosis of major depressive disorder, as determined by the Structured Clinical Interview for Diagnosis, who sought mental health treatment at outpatient clinics. Additional instruments were administered to 134 newly admitted adults who had been taking a prescribed antidepressant medication for at least a week to assess perceived stigma, self-rated severity of illness, and views about treatment. The patients were reinterviewed three months later and were classified as adherent or nonadherent on the basis of self-reported estimates of the number and frequency of missed doses., Results: Medication adherence was associated with lower perceived stigma, higher self-rated severity of illness, age over 60 years, and absence of personality pathology. No other characteristics of treatment or illness were significantly related to medication adherence., Conclusions: Perceived stigma associated with mental illness and individuals' views about the illness play an important role in adherence to treatment for depression. Clinicians' attention to psychological barriers early in treatment may improve medication adherence and ultimately affect the course of illness.