Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease.

BACKGROUND: Ozanimod showed efficacy and safety in the phase 2 STEPSTONE study conducted in patients with moderately to severely active Crohn's disease. AIMS: This analysis assessed the effects of ozanimod on circulating lymphocytes in Crohn's disease. METHODS: Patients received ozanimod 0.92 mg for 12 weeks. Lymphocyte subtypes were evaluated using multicolor flow analysis on blood samples collected before treatment and on Week 12. Absolute lymphocyte count changes were analyzed by Wilcoxon signed rank tests. Disease activity changes and efficacy outcomes were evaluated at Week 12, and associations with lymphocyte subtype levels were assessed using Spearman's correlation and logistic regression. RESULTS: Reductions in median total T, Th, and cytotoxic T cells occurred at Week 12 (45.4%-76.8%), with reductions in most subtypes of 47.5% to 91.3% (P < 0.001). CD8+ terminally differentiated effector memory cells were largely unaffected (median change, - 19%; P = 0.44). Reductions in median total B cells occurred at Week 12 (76.7%), with reductions in subtypes of 71.4% to 81.7% (P < 0.001). Natural killer and monocyte cell counts were unchanged. Greater baseline levels and changes in nonswitched memory B cells were significantly associated with clinical, endoscopic, and histologic efficacy (P < 0.05, all comparisons). CONCLUSIONS: Ozanimod reduced circulating levels of all B-cell and most T-cell subsets but not monocytes or natural killer cells. Key subsets relevant to immune surveillance were not reduced, supporting the low risk of infection and malignancy with ozanimod in chronic inflammatory diseases. Levels of nonswitched memory B cells were associated with efficacy, providing a potential marker for ozanimod response. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02531113, EudraCT: 2015-002025-19.

SARS-CoV-2 vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis.

OBJECTIVE: To investigate the serologic response, predictors of response, and clinical outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection in ozanimod-treated participants with relapsing multiple sclerosis (RMS) from DAYBREAK. METHODS: DAYBREAK (ClinicalTrials.gov-NCT02576717), an open-label extension study of oral ozanimod 0.92 mg, enrolled participants aged 18-55 years with RMS who completed phase 1-3 ozanimod trials. Participants who were fully vaccinated against SARS-CoV-2 with mRNA or non-mRNA vaccines, were unvaccinated, and/or had COVID-19-related adverse events (AEs, with or without vaccination) and postvaccination serum samples were included (n = 288). Spike receptor binding domain (RBD) antibody levels (seroconversion: ≥0.8 U/mL) and serologic evidence of SARS-CoV-2 infection (nucleocapsid IgG: ≥1 U/mL) were assessed (Roche Elecsys/Cobas e411 platform). RESULTS: In fully vaccinated participants (n = 148), spike RBD antibody seroconversion occurred in 90% (n = 98/109) of those without serologic evidence of prior SARS-CoV-2 exposure (100% [n = 80/80] seroconversion after mRNA vaccination) and in 100% (n = 39/39) of participants with serologic evidence of viral exposure. mRNA vaccination predicted higher spike RBD antibody levels, whereas absolute lymphocyte count (ALC), age, body mass index, and sex did not. COVID-19-related AEs were reported in 10% (n = 15/148) of fully vaccinated participants-all were nonserious and not severe; all participants recovered. INTERPRETATION: Most ozanimod-treated participants with RMS mounted a serologic response to SARS-CoV-2 vaccination and infection, regardless of participant characteristics or ALC levels. In this analysis, all COVID-19-related AEs post-full vaccination in participants taking ozanimod were nonserious and not severe.

Five-week yin yoga-based interventions decreased plasma adrenomedullin and increased psychological health in stressed adults: A randomized controlled trial.

BACKGROUND: Non-communicable diseases (NCDs, e.g. cardiovascular disease) are responsible for high rates of morbidity and the majority of premature deaths worldwide. It is necessary to develop preventative interventions that can reduce the associated risk factors of NCDs. Researchers have found that the biomarker adrenomedullin (ADM) becomes elevated years before the onset of NCDs and might play an important role in their development. ADM has also been linked to psychological problems such as stress, anxiety, and depression, which are known risk factors of NCDs. In this randomized controlled trial, we examined whether participating in a five-week yoga intervention reduces ADM and increases psychological health in middle-aged adults who self-report as moderately to highly stressed, but who otherwise exhibit no physical complaints. METHODS: One hundred and five adults (78% women; mean age = 53.5, SD = 6.7) were randomly assigned to (1) a five-week Yin yoga intervention, (2) a five-week intervention combining Yin yoga with psychoeducation and mindfulness practice (called the YOMI program), or (3) a control group who did not practice yoga or mindfulness for five weeks. RESULTS: Compared to the control group, we observed significantly greater pre-post reductions in plasma ADM levels (p < .001), anxiety (p ≤ .002), and sleep problems (p ≤ .003) in both intervention groups. Furthermore, the YOMI group exclusively showed significantly greater pre-post reductions in stress (p = .012) and depression (p = .021) compared to the control group. Significant correlations (p < .05) were found between pre-post reductions in ADM and anxiety symptoms (p = .02) and depression (p = .04) in the entire sample. CONCLUSION: The five-week Yin yoga-based interventions appeared to reduce both the physiological and psychological risk factors known to be associated with NCDs. The study suggests that incorporating Yin yoga could be an easy and low-cost method of limiting the negative health effects associated with high stress. TRIAL REGISTRATION: ClinicalTrials.gov NCT03428542.

The effects of yoga on stress and psychological health among employees: an 8- and 16-week intervention study.

BACKGROUND: The stresses of modern work life necessitate effective coping strategies that are accessible and affordable to the general public. Yoga has been found to reduce stress in clinical samples, but studies are needed to examine standard gym yoga classes among functional individuals. OBJECTIVES: This study investigated the effects of 8- and 16-week gym yoga on stress and psychological health. DESIGN AND METHOD: Ninety individuals reporting moderate-to-high stress were randomly assigned to 16 consecutive weeks of yoga, or to a waitlist crossover group who did not practice yoga for 8 weeks then practiced yoga for 8 weeks. Stress and psychological health variables were assessed at baseline, 8 weeks, and 16 weeks. RESULTS: Significant reductions in stress and all psychological health measures were found within the Yoga group over 16 weeks. When compared to the control group, yoga practitioners showed significant decreases in stress, anxiety, and general psychological health, and significant increases in well-being. The group who did not practice yoga showed significant decreases in stress, anxiety, depression, and insomnia after they crossed over and practiced yoga for 8 weeks. CONCLUSIONS: Gym yoga appears to be effective for stress amelioration and promotion of psychological health among workers experiencing stress.

A case of depressive personality disorder: aligning theory, practice, and clinical research.

Depressive personality disorder (DPD) is highly studied and common in clinical settings. Nevertheless, it is rife with controversies and often overshadowed by major depression and dysthymia with which it shares many similarities but also is clinically distinct. Possibly as a result, DPD is underdiagnosed and misunderstood in clinical care. Thus the goal of this practice review is to present a case from psychiatric clinical work illustrating how DPD may be commonly overlooked in routine care, and how the conceptualization of this case and its treatment plan changed course once DPD was considered by treating staff, ultimately contributing to the successful outcome of the case. Questions elicited by the case are subsequently discussed in the context of the empirical literature on DPD, allowing for a clearer picture to emerge on DPD and its role in the development, course, and treatment of depression.

Mood and Global Symptom Changes among Psychotherapy Clients with Depressive Personality.

The present study assessed the rate of depressive personality (DP), as measured by the self-report instrument depressive personality disorder inventory (DPDI), among 159 clients entering psychotherapy at an outpatient university clinic. The presenting clinical profile was evaluated for those with and without DP, including levels of depressed mood, other psychological symptoms, and global severity of psychopathology. Clients were followed naturalistically over the course of therapy, up to 40 weeks, and reassessed on these variables again after treatment. Results indicated that 44 percent of the sample qualified for DP prior to treatment, and these individuals had a comparatively more severe and complex presenting disposition than those without DP. Mixed-model repeated-measures analysis of variance was used to examine between-groups changes on mood and global severity over time, with those with DP demonstrating larger reductions on both outcome variables, although still showing more symptoms after treatment, than those without DP. Only eleven percent of the sample continued to endorse DP following treatment. These findings suggest that in routine clinical situations, psychotherapy may benefit individuals with DP.

The Swedish Depressive Personality Disorder Inventory: psychometrics and clinical correlates from a DSM-IV and proposed DSM-5 perspective.

BACKGROUND: Depressive personality is commonly seen in clinical practice, and today only one exclusive self-report instrument-the Depressive Personality Disorder Inventory (DPDI)-is available for its assessment based on the DSM-IV description of the construct. AIMS: The purpose of this research was to evaluate a Swedish version of this measure (DPDI-Swe) in terms of its reliability, internal structure, and convergent validity using related variables from the DSM-IV criteria for depressive personality disorder (DPD) and the proposed DPD trait set for DSM-5. METHODS: A non-clinical sample of 255 adults in southern Sweden completed a self-report package, which, in addition to DPD, included the assessment of self-esteem, optimism, hope, rumination, worry, depression, and anxiety. Quality of life was also measured. RESULTS: Results indicated that the DPDI-Swe was internally consistent (α = 0.96). Exploratory factor analysis with oblique rotation yielded three components, together accounting for 48.21% of the variance in DPDI-Swe scores. There were strong positive associations between the DPDI-Swe and measures of depression, anxiety, rumination, and worry, and strong negative associations between the DPDI-Swe and measures of self-esteem, optimism, hope, and quality of life. These significant relationships remained, albeit slightly diminished, after statistically controlling for current depressed mood. CONCLUSIONS AND CLINICAL IMPLICATIONS: The DPDI-Swe appears to be a reliable and valid measure of DPD, and it is available for clinical and research use.

A structural validation of an inventory based on the Abridged Five Factor Circumplex Model (AB5C).

We investigated the structural validity of an inventory from the International Personality Item Pool (Goldberg et al., 2006) that is based on the Abridged Five Factor Circumplex (AB5C) model. In a Swedish sample of 1,080 subjects using confirmatory factor analysis, we found that the majority of investigated facets had a primary loading on 1 of the 5 personality factors and a secondary loading on another factor. These results provide overall support for the inventory and indirect support for the AB5C model. Some of the problems detected in the inventory appear to be rooted at the item level and may be a result of how the AB5C is operationalized. Thus, the inventory still requires some refinement and is not in its final stage of development. Nevertheless, our preliminary results are very promising, and we believe the AB5C model deserves renewed attention in trait psychology.

Select comorbid personality disorders and the treatment of chronic depression with nefazodone, targeted psychotherapy, or their combination.

BACKGROUND: Individuals with chronic depression respond poorly to both medication and psychotherapy. The reasons for the poorer response, however, remain unclear. One potential factor is the presence of comorbid Axis II personality disorders (PDs), which occur at high rates among these patients. METHODS: This study examines the moderating influence of co-occurring PDs, primarily in cluster C, among 681 chronically depressed adult outpatients who were randomly assigned to 12 weeks of treatment with nefazodone, a specialized psychotherapy for chronic depression, or their combination. RESULTS: At baseline, 50.4% (n=343) of patients met criteria for one or more Axis II disorders. Following 12 weeks of treatment, patients with comorbid PDs had statistically lower depression scores (M=12.2, SD=+9.2) than patients without comorbid PDs (M=13.5, SD=+8.7). There was no differential impact of a comorbid PD on responsiveness to medication versus psychotherapy. The results did not change when the data were analyzed using an intent-to-treat sample or when individual personality disorders were examined separately. LIMITATIONS: Patients with severe borderline, antisocial, and schizotypal PDs were excluded from study entry; therefore, these data primarily apply to patients with cluster C PDs and may not generalize to other Axis II conditions. CONCLUSIONS: Comorbid Axis II disorders did not negatively affect treatment outcome and did not differentially affect response to psychotherapy versus medication. Treatment formulations for chronically depressed patients with certain PDs may not need to differ from treatment formulations of chronically depressed patients without co-occurring PDs.

Clinical features and functioning of patients with minor depression.

BACKGROUND: The two essential features of minor depression are that it has fewer symptoms than major depression and that it is less chronic than dysthymia. This study describes the clinical features and functioning of outpatients with minor depression. METHODS: Subjects with minor depression (with and without a prior history of major depression) were recruited through clinical referrals and community advertising. Assessments included the Structured Clinical Interview for DSM-IV (SCID), the 17-item Hamilton Rating Scale for Depression (HAM-D), the Inventory of Depressive Symptomatology-Self Report (IDS-SR) and Clinician Rated (IDS-C) scales, the Global Assessment of Functioning (GAF) scale, the Medical Outcomes Study 36-item Short-Form scale (MOS), and the Clinical Global Impressions Severity Scale (CGI). Data from previously published studies of major depression, minor depression, and normal controls were compared to our data set. RESULTS: Minor depression is characterized primarily by mood and cognitive symptoms rather than vegetative symptoms; the functional impairment associated with minor depression is as severe as for major depression in several areas; minor depression occurs either independently of major depression or as a stage of illness during the long-term course of major depression, and minor depression patients with and without a history of major depression have similar levels of depressive severity and functional impairment. CONCLUSIONS: These findings support the notion that minor depression is an important clinical entity that fits within the larger spectrum of depressive disorders.

The effects of celecoxib augmentation on cytokine levels in schizophrenia.

Celecoxib augmentation therapy has been reported to enhance the rate of clinical response for patients with schizophrenia. This may be due in part to an effect of celecoxib in the immune dysfunction associated with schizophrenia. Given concerns about the safety of COX-2 inhibitors, studies investigating cytokine levels in medicated patients with schizophrenia are of public health importance. Twenty-eight schizophrenia subjects stabilized on olanzapine or risperidone were randomized to receive 8 wk of celecoxib (400 mg/d) or placebo. Serum soluble IL-2 receptor (sIL-2r) and in-vitro PHA-stimulated whole-blood cytokine production levels were measured at baseline, 1 wk, and 8 wk. Celecoxib augmentation did not alter any of the cytokine parameters measured for the overall study group. However, 1 wk of celecoxib augmentation increased TNF-alpha and IL-2 production levels in olanzapine-treated subjects. These elevations did not persist by week 8. Overall, celecoxib does not significantly modify cytokine levels in medicated schizophrenia subjects.

Celecoxib augmentation of continuously ill patients with schizophrenia.

BACKGROUND: Previous reports have demonstrated a beneficial effect of celecoxib adjunctive therapy for patients with an acute exacerbation of schizophrenia. We investigated the effects of celecoxib augmentation of atypical antipsychotic medications for continuously symptomatic outpatient subjects with schizophrenia to further extend these findings. We hypothesized that celecoxib augmentation therapy would improve psychopathology ratings compared with placebo. METHODS: Thirty-eight symptomatic outpatient subjects meeting DSM-IV criteria for schizophrenia and on a stable dose of an atypical antipsychotic medication for at least three months were randomized to receive 8 weeks of double blind placebo or celecoxib (400 mg/day) augmentation. Measures of psychopathology, functional disability, and extrapyramidal side effects were performed throughout the study. RESULTS: The treatment cohorts did not differ on any of the clinical outcome measures. CONCLUSIONS: Celecoxib augmentation of continuously ill outpatient subjects with schizophrenia did not improve clinical symptoms or measures of disability.

Quality of life in geriatric patients with mood and anxiety disorders.

This article reviews the impact of depressive and anxiety disorders on quality of life (QOL), disability, and economic burden in the lives of older individuals. Distinctions between the terms QOL, disability, and burden are important in understanding the extent of improvement needed in treatment for elderly patients with depression or anxiety. Treatment efforts should be extended to remediate not only signs and symptoms of psychiatric syndromes but QOL and disability as well; increased understanding toward this end is evolving, yet it is clear that these issues need to be the focus of more investigation.

Challenges in the development of clinical trials for major depressive disorder: lessons learned from trials in minor depression.

This paper reviews some of the challenges faced by individuals who design and implement clinical trials of potential antidepressant medications. Particular emphasis is placed on questioning the validity of some of the theoretical assumptions that form the underpinnings of most conventional trials. Work from our group developing clinical trial methodology for minor depression is used as an example of how alternate constructs may be helpful to differentiate drug-placebo differences.

Long-term antidepressant treatment.

Major depressive disorder (MDD) is a common and costly illness. Recent research suggests that MDD is a lifelong condition for many patients. This has stimulated researchers to identify risk factors associated with an increased frequency of relapse and recurrence of major depression. One of the most important of these risk factors is an incomplete response to acute treatment. These data have led investigators to pursue techniques that enhance the acute response of patients to therapy, and study whether long-term treatment with antidepressants may prevent relapse and recurrence of MDD. Data from these trials suggest that continuation and maintenance treatment of MDD confers some protection against deteriorating back into an episode after acute treatment and against developing another episode of MDD.