Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers. METHODS: To clarify, we measured inflammatory markers in patients with MDD with and without high levels of suicidal ideation and in nondepressed controls (N = 124). Levels of suicidal ideation, depression severity, and recent suicide attempts were assessed by structured clinical interviews. A composite score including the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and C-reactive protein (CRP) was used as an inflammatory index. Analysis of covariance models were used to assess group differences with adjustments for age and gender. RESULTS: Patients with MDD and high suicidal ideation had significantly higher inflammatory index scores than both controls, F(1,53) = 18.08, partial η(2) = .25, P < .001, and patients with MDD and lower suicidal ideation F(1,44) = 7.59, partial η(2) = .15, P = .009. In contrast, patients with lower suicidal ideation were not significantly different from controls on the inflammatory index, F(1,63) = .52, partial η(2) = .01, P = .47. Follow-up analyses indicated that differences between patients with MDD and high versus lower suicidal ideation were independent of depression severity and recent suicide attempts. CONCLUSIONS: Suicidal ideation may be uniquely associated with inflammation in depressed patients.

Psychedelic perceptions: mental health service user attitudes to psilocybin therapy.

INTRODUCTION: Despite the rapid advance of psychedelic science and possible translation of psychedelic therapy into the psychiatric clinic, very little is known about mental health service user attitudes. OBJECTIVES: To explore mental health service user attitudes to psychedelics and psilocybin therapy. METHODS: A questionnaire capturing demographics, diagnoses, previous psychedelic and other drug use, and attitudes to psychedelics and psilocybin therapy was distributed to mental health service users. RESULTS: Ninety-nine participants completed the survey (52% female, mean age 42 years). The majority (72%) supported further research, with 59% supporting psilocybin as a medical treatment. A total of 27% previously used recreational psilocybin, with a male preponderance (p = 0.01). Younger age groups, those with previous psychedelic experience, and those with non-religious beliefs were more likely to have favourable attitudes towards psilocybin. A total of 55% of the total sample would accept as a treatment if doctor recommended, whereas 20% would not. Fewer people with depression/anxiety had used recreational psychedelics (p = 0.03) but were more likely to support government funded studies (p = 0.02). A minority (5%) of people with conditions (psychosis and bipolar disorder) that could be exacerbated by psilocybin thought it would be useful for them. One fifth of the total sample viewed psychedelics as addictive and unsafe even under medical supervision. Concerns included fear of adverse effects, lack of knowledge, insufficient research, illegality, and relapse if medications were discontinued. CONCLUSIONS: The majority supported further research into psilocybin therapy. Younger people, those with previous recreational psychedelic experience, and those with non-religious beliefs were more likely to have favourable attitudes towards psilocybin therapy.

Outcome of First-admission Depression Treated in a Specialized Mood Disorders Service.

OBJECTIVE: Few studies have described the treatment or outcome of depression in specialized mood disorders units (MDUs). Previous studies have focused on cohorts of patients with highly treatment-resistant illness who are likely to have a poor prognosis even with intensive treatment. This study describes the treatment and medium-term outcomes of a cohort of first-admission depressed patients with less treatment-resistant illness treated in a specialized MDU. METHODS: A cohort of 137 consecutive first-admission depressed patients, referred to an MDU over 2 years, were interviewed using standardized schedules and followed up prospectively from admission for ∼18 months to describe baseline characteristics, treatment, outcome, and predictors of outcome. Times to recovery and recurrence were evaluated using survival analyses and predictors of outcome were examined using bivariate and multivariate regression analyses. RESULTS: On admission, 75% of the 137 patients had depression that had been found to be resistant to pharmacological treatment, and 34% had been chronically depressed (>2 y). Over half of the patients had likely maladaptive personality traits and one third had at least 1 comorbid psychiatric disorder. By discharge, a significantly higher proportion of the patients were being prescribed very high (P<0.01) or high doses (P<0.05) of antidepressants, augmentation therapy (P<0.001), or a combination of antidepressants (P<0.001) or were engaged in individual psychotherapy (P<0.001), compared with baseline. With intensive treatment, 62% of the patients recovered by 6 months and 76% by 12 months, with 83% overall recovering and patients found to be asymptomatic during almost 60% of the follow-up period. However, 48% suffered a recurrence over the course of the follow-up. Chronicity of mood episodes (P<0.01) and the presence of psychiatric comorbidity (P<0.05) predicted recurrence. CONCLUSIONS: This prospective, naturalistic, medium-term study describes better outcomes, in terms of recovery and symptomatology over time, in a cohort of first-admission depressed patients than previous first-admission studies after continuous, intensive treatment, although the proportion of patients who experienced recurrences remained high.

Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy.

BACKGROUND: Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT. METHODS: 55 melancholic depressed patients and 26 controls participated. 33 patients (60%) were referred for ECT. Blood samples were taken at baseline, one hour after the first ECT session, and 48h after ECT series completion. RESULTS: At baseline, melancholic depressed patients had significantly higher levels of the pro-inflammatory cytokine IL-6, and lower levels of the regulatory cytokine TGF-ß than controls. A significant surge in IL-6 levels was observed one hour after the first ECT session, but neither IL-6 nor TGF-ß levels normalized after completion of ECT series. Seventy per cent (n=23) of ECT recipients showed clinical response and 42% (n=10) reached remission. Neither IL-6 nor TGF-ß changes correlated with clinical improvement following ECT. No significant changes in IL-10, TNF-α and CRP levels were found in relation to melancholia or response to ECT. LIMITATIONS: As a naturalistic study, some potential confounders could not be eliminated or controlled, including medication use. CONCLUSIONS: Melancholic depressed patients demonstrated a peripheral increase in IL-6 and reduction in TGF-ß, which did not normalize despite clinical response to ECT. These findings may be consistent with emerging hypotheses of the role of inflammation in mediating neurotrophin expression. The implications of chronic inflammation in the melancholic depressed population for future medical health, particularly cardiovascular risk, are largely unknown and warrant further investigation.

Recovery from mental illness: changing the focus of mental health services.

The concept of recovery entered the lexicon of the mental health services in the 1980s following the publication of a series of studies and personal narratives which demonstrated that the course of mental illness was not always one of inevitable deterioration and that people diagnosed with severe mental illness could reclaim or recover meaningful lives. For a long time, recovery was not thought possible by many family members, service providers and researchers. However globally, specific policy and clinical strategies are being developed to implement recovery principles although key questions remain. In fact, the possibility of recovery is still debated by some. In this paper, we include information about the recovery model and the medical model; we provide evidence for recovery and document changes in mental health practices and policies incorporating recovery as the guiding principle. We also attempt to address the debate as to whether recovery is an evidence based practice. We propose that evidence based practice should be complementary to value-based and narrative-based practices and we suggest an integrative model that maximises the virtues and minimises the weaknesses of each practices (see Figure 1).

Electroconvulsive therapy: International guidelines, clinical governance and patient selection.

Recent reports from the Inspector of Mental Health Services have highlighted marked variations in electroconvulsive therapy (ECT) prescriptions nationally. This article reviews six international guidelines in order to assess the question of which patients should be referred for ECT treatment and at what stage in their illness. The guidelines display a general consensus in terms of the acutely and severely ill, but differ dramatically in terms of access to ECT outside this category, such as the moderately depressed patient who is treatment resistant but non-psychotic and non-suicidal and who requests ECT due to a previous good response. The American Psychiatric Association guidelines strongly support the early consideration and use of ECT, highlighting the dangers associated with increased length of illness for individual prognosis. The National Institute of Clinical Excellence (UK) guidelines are the strictest, reserving ECT for the severely ill exclusively and only in cases with a demonstrable failure of alternative treatments. This confusion may ultimately need to be addressed by the Mental Health Commission as data relating to variations in practice may result in inappropriate reductions in access to an established treatment.

Translation enhancement by optimized downstream box sequences in Escherichia coli and Mycobacterium smegmatis.

The effect on translation of downstream box sequences optimized for binding to Mycobacterium smegmatis and Escherichia coli 16S rRNA in the absence of a Shine-Dalgarno (SD) region was investigated. The relative translational efficiency of each construct in either M. smegmatis or E. coli was determined. Eradication of the SD region in the absence of a downstream box abolished the translation activity. In contrast, optimized downstream box constructs resulted in a 13- and 18-fold increase in protein synthesis, relative to non-optimized DB controls in E. coli and M. smegmatis, respectively.