Recent functional neuroimaging studies suggest that the brain networks responsible for time processing are involved during other cognitive processes, leading to a hypothesis that time-related processing is needed to perform a range of tasks across various cognitive functions. To examine this hypothesis, we analyze whether, in healthy subjects, the brain structures activated or deactivated during performance of timing and oddball-detection type tasks coincide. To this end, we conducted two independent signed differential mapping (SDM) meta-analyses of functional magnetic resonance imaging (fMRI) studies assessing the cerebral generators of the responses elicited by tasks based on timing and oddball-detection paradigms. Finally, we undertook a multimodal meta-analysis to detect brain regions common to the findings of the two previous meta-analyses. We found that healthy subjects showed significant activation in cortical areas related to timing and salience networks. The patterns of activation and deactivation corresponding to each task type partially coincided. We hypothesize that there exists a time and change-detection network that serves as a common underlying resource used in a broad range of cognitive processes.

After publication of our article [1] we have been notified that Table 2 was incorrectly formatted.

BackgroundAn inverse association between total leisure-time physical activity (LTPA) and depression has been previously documented in the scientific literature. Our objective was to prospectively assess the association of LTPA with the risk of depression, focusing on several dimensions of LTPA (intensity, duration and type).MethodsThe SUN (Seguimiento Universidad de Navarra) project is a prospective cohort study formed by Spanish university graduates. A total of 15,488 adults (40.2% men, mean age 3712years) initially free of depression were assessed. A report of a validated medical diagnosis of depression or the habitual use of antidepressants (any of both) were considered as incident cases of depression. LTPA was estimated through previously validated self-reported questionnaires. Participants were classified following Physical Activity recommendations from the World Health Organization, and according to the intensity, duration and type of LTPA. Cox proportional hazards regression models were run, adjusted for demographic, lifestyle, and dietary factors, to estimate adjusted hazard ratios (HR) of depression and 95% confidence intervals (CI).ResultsDuring 163,059 person-years of follow-up we registered 870 incident cases of depression. Participants with higher total LTPA (METs-h/wk) and higher duration of LTPA (hours/wk) exhibited a lower risk of depression HR=0.84 (95% CI: 0.72-0.99) and HR=0.83 (0.70-0.99) respectively, whereas intensity of LTPA (MET) did not show any association with depression.Conclusion p id=Par Participants with higher LTPA had a lower risk of depression. The inverse association was stronger for total LPTA time than for its intensity. Higher duration of LTPA should be encouraged to prevent depression.

Dysthymia or persistent depressive disorder is an affective disorder of chronic course and lower intensity than major depression. Its onset is insidious and usually appears in youth. The presence of a depressed mood for at least two years, along with other symptoms such as sleep disturbances, low self-esteem, poor concentration or fatigue are features of this disorder. Sometimes, major depressive disorder is superimposed on an underlying dysthymia («double depression»). Diagnosis is clinical, being essential differential diagnosis from other entities (major depression, personality disorders, substances and drugs abuse). Combination of antidepressants and psychotherapy is the most effective treatment.

Objective: About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants. This study compared the efficacy and safety of switching patients with treatment-resistant depression from an ineffective antidepressant to flexibly dosed esketamine nasal spray plus a newly initiated antidepressant or to a newly initiated antidepressant (active comparator) plus placebo nasal spray. Methods: Thiswas a phase 3, double-blind, active-controlled, multicenter study conducted at 39 outpatient referral centers. The study enrolled adults with moderate to severe nonpsychotic depression and a history of nonresponse to at least two antidepressants in the current episode, with one antidepressant assessed prospectively. Confirmed nonresponders were randomly assigned to treatment with esketamine nasal spray (56 or 84 mg twice weekly) and an antidepressant or antidepressant and placebo nasal spray. The primary efficacy endpoint, change from baseline to day 28 in MontgomeryAsberg Depression Rating Scale (MADRS) score, was assessed by a mixed-effects model using repeated measures. Results: Of 435 patients screened, 227 underwent randomization and 197 completed the 28-day double-blind treatment phase. Change in MADRS score with esketamine plus antidepressant was significantly greater than with antidepressant plus placebo at day 28 (difference of least square means=24.0, SE=1.69, 95% CI=27.31, 20.64); likewise, clinically meaningful improvement was observed in the esketamine plus antidepressant arm at earlier time points. The five most common adverse events (dissociation, nausea, vertigo, dysgeusia, and dizziness) all were observed more frequently in the esketamine plus antidepressant arm than in the antidepressant plus placebo arm; 7% and 0.9% of patients in the respective treatment groups discontinued study drug because of an adverse event. Adverse events in the esketamine plus antidepressant arm generally appeared shortly after dosing and resolved by 1.5 hours after dosing. Conclusions: Current treatment options for treatmentresistant depression have considerable limitations in terms of efficacy and patient acceptability. Esketamine is expected to address an unmet medical need in this population through its novel mechanism of action and rapid onset of antidepressant efficacy. The study supports the efficacy and safety of esketamine nasal spray as a rapidly acting antidepressant for patients with treatment-resistant depression.

IMPORTANCE Controlled studies have shown short-term efficacy of esketamine for treatment-resistant depression (TRD), but long-term effects remain to be established. OBJECTIVE To assess the efficacy of esketamine nasal spray plus an oral antidepressant compared with an oral antidepressant plus placebo nasal spray in delaying relapse of depressive symptoms in patients with TRD in stable remission after an induction and optimization course of esketamine nasal spray plus an oral antidepressant. DESIGN, SETTING, AND PARTICIPANTS In this phase 3, multicenter, double-blind, randomized withdrawal study conducted from October 6, 2015, to February 15, 2018, at outpatient referral centers, 705 adults with prospectively confirmed TRD were enrolled; 455 entered the optimization phase and were treated with esketamine nasal spray (56 or 84 mg) plus an oral antidepressant. After 16 weeks of esketamine treatment, 297 who achieved stable remission or stable response entered the randomized withdrawal phase. INTERVENTIONS Patients who achieved stable remission and those who achieved stable response (without remission) were randomized 1:1 to continue esketamine nasal spray or discontinue esketamine treatment and switch to placebo nasal spray, with oral antidepressant treatment continued in each group. MAIN OUTCOMES AND MEASURES Time to relapse was examined in patients who achieved stable remission, as assessed using a weighted combination log-rank test. RESULTS Among the 297 adults (mean age [SD], 46.3 [11.13] years; 197 [66.3%] female) who entered the randomized maintenance phase, 176 achieved stable remission; 24 (26.7%) in the esketamine and antidepressant group and 39 (45.3%) in the antidepressant and placebo group experienced relapse (log-rank P=.003, number needed to treat [NNT], 6). Among the 121 who achieved stable response, 16 (25.8%) in the esketamine and antidepressant group and 34 (57.6%) in the antidepressant and placebo group experienced relapse (log-rank P<.001, NNT, 4). Esketamine and antidepressant treatment decreased the risk of relapse by 51% (hazard ratio [HR], 0.49; 95% CI, 0.29-0.84) among patients who achieved stable remission and 70% (HR, 0.30; 95% CI, 0.16-0.55) among those who achieved stable response compared with antidepressant and placebo treatment. The most common adverse events reported for esketamine-treated patients after randomization were transient dysgeusia, vertigo, dissociation, somnolence, and dizziness (incidence, 20.4%-27.0%), each reported in fewer patients (<7%) treated with an antidepressant and placebo. CONCLUSIONS AND RELEVANCE For patients with TRD who experienced remission or response after esketamine treatment, continuation of esketamine nasal spray in addition to oral antidepressant treatment resulted in clinically meaningful superiority in delaying relapse compared with antidepressant plus placebo.

BackgroundThe role of dietary patterns in the prevention of unipolar depression has been analyzed in several epidemiological studies. The primary aims of this study are to determine the effectiveness of an extra-olive oil-enriched Mediterranean diet in reducing the recurrence of depression and improving the symptoms of this condition.MethodsMulticenter, two-arm, parallel-group clinical trial. Arm 1, extra-virgin olive oil Mediterranean diet; Arm 2, control group without nutritional intervention. Dieticians are in charge of the nutritional intervention and regular contact with the participants. Contacts are made through our web platform (https://predidep.es/participantes/) or by phone. Recurrence of depression is assessed by psychiatrists and clinical psychologists through clinical evaluations (semi-structured clinical interviews: Spanish SCID-I). Depressive symptoms are assessed with the Beck Depression Inventory. Information on quality of life, level of physical activity, dietary habits, and blood, urine and stool samples are collected after the subject has agreed to participate in the study and once a year.DiscussionTo the best of our knowledge, the PREDI-DEP trial is the first ongoing randomized clinical trial designed to assess the role of the Mediterranean diet in the prevention of recurrent depression. It could be a cost-effective approach to avoid recurrence and improve the quality of life of these patients.Trial registrationThe study has been prospectively registered in the U.S. National Library of Medicine (https://clinicaltrials.gov) with NCT number: NCT03081065.

Interest in the relationship between nutritional epidemiology and the risk of mental illness is growing. So, some reports have described a lower risk of depression related with certain dietary patterns. In turn, the relationship between cardiovascular and depression risk is better known. Because their prevalence and severity, is urgent to implement hygienic-dietetic measures in disorders like major depression. The intake of specific nutrients, the adherence to healthy eating patterns and a lower presence of cardiovascular risk factors have been related with a lower risk of depression. A healthy diet, rich in fruit, vegetables, olive oil, nuts and low in meats, trans fats, added sugars and sugary drinks, among others, has been proposed. A reduction of the depressive symptoms has been associated to the adherence to high quality diet (like Mediterranean diet, among others).

When adequate therapeutic measures are implemented, the response rates of depressive disorders, despite being a major cause of discomfort, disability and suicide, are acceptable. Diagnosis is based on anamnesis, detailed psychopathological exploration and data collection from third persons, if possible. In order to rule out general medical conditions, complementary tests can be requested. It is mandatory to determine the severity of the condition by assessing the impact of the symptoms and the risk of harm to oneself or third parties. Treatment has to be consistent with the severity of symptoms, personalized to each patient and based on scientific evidence. Hygienic-dietetic guides, psychotherapy, pharmacological treatments, neuromodulation therapies and functional rehabilitation, are included in the therapeutic measures. Two algorithms for clinical decision making are included in the present protocol.