Significance of REM Sleep in Depression: Effects on Neurogenesis

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Developmental pathways towards mood disorders in adult life: Is there a role for sleep disturbances?

Introduction: Mood disorders are among the most prevalent and serious mental disorders and rank high among to the leading global burdens of disease. The developmental psychopathology framework can offer a life course perspective on them thus providing a basis for early prevention and intervention. Sleep disturbances, are considered risk factors for mood disorders across childhood, adolescence and adulthood. Assuming that sleep disturbances may play a pivotal role in the pathogenesis of mood disorders from a life course point of view, we reviewed the data on developmental pathways towards mood disorders in adult life in relation to sleep disturbances. Method: From February 2017, a systematic search was conducted in PubMed, PsycINFO and Embase electronic databases for literature on developmental pathways to mood disorders in adult life in relation to sleep disturbances and to 1) pre-natal stress, 2) early brain developmental processes, and 3) temperaments, character and attachment style. Results: Eleven, 54 and 15 articles were respectively selected. Conclusions: Experimental and clinical studies revealed that exposure to prenatal/early life stress results in sleep disturbances such as poor sleep and altered circadian regulation phases and may predict or even precipitate mood disorders in adulthood. Chronic sleep disruption may interfere with neuronal plasticity, connectivity and the developing brain thus contributing to the development of mood disorders. In addition sleep and circadian dysregulations have been shown to be related to those temperaments, character and attachment styles which are considered precursors of mood disorders. Sleep and circadian behaviours may serve as early targets regarding mood disorders

Insomnia symptoms predict emotional dysregulation, impulsivity and suicidality in depressive bipolar II patients with mixed features

Introduction: Insomnia symptoms are very common in Bipolar Disorder. Our aim was to assess the potential association between insomnia, emotion dysregulation and suicidality in subjects with Bipolar Disorder. Methods: Seventy-seven subjects with Bipolar Disorder type II with a depressive episode with mixed features were recruited. Patients were assessed with SCID-DSM-5, the Insomnia Severity Index (ISI), the Difficulties in Emotion Regulation Scale (DERS), the Scale for Suicide Ideation (SSI) while evaluating manic and depressive symptoms. Results: Subjects with insomnia symptoms compared to those without showed higher scores in the DERS scale and subscales, including impulsivity, and in the SSI scale. Insomnia symptoms significantly predicted the severity of depressive symptoms, emotion dysregulation, and suicidality in subjects with bipolar disorder. In particular, insomnia was related to difficulties in some areas of emotion regulation including impulsivity. Emotion dysregulation significantly mediated the association between insomnia and depressive symptoms (Z = 2.9, p = 0.004). Furthermore, emotional impulsivity mediated the association between insomnia symptoms and suicidality (Z = 2.2, p = 0.03). Conclusion: In our study, subjects with bipolar disorder suffering from insomnia experienced a greater severity of depressive symptoms and suicidality compared to subjects without insomnia. Insomnia was associated with emotion dysregulation, impulsivity and suicidality. Further research is necessary to investigate if these latter features may benefit from early insomnia treatment in subjects with bipolar disorder

Attitude toward prescription and clinical monitoring of lithium salts in a sample of Italian psychiatrists: preliminary data

Results of international prescribing patterns show that lithium prescription and biochemical drug monitoring seem to differ from a country to another. In spite of clear-cut supporting scientific evidence lithium monitoring is often disregarded, incorrectly used or underused. In Italy the trend of lithium prescriptions and biochemical monitoring is far from what suggested in guidelines; even if there's an impressive paucity of data about lithium monitoring and related iatrogenic risks in our country. In order to assess the current attitude in Italy toward lithium treatment in bipolar disorder we asked to a number of senior psychiatrists, working within the national territory, to fill a 34 items interview. Items were grouped in 8 domains, ranging from prescription pattern to therapeutic drug monitoring and other safety measures to prevent iatrogenic harm during lithium therapy. A preliminary analysis of the very first data, collected mainly in Tuscany, suggested that overall knowledge about lithium prescription and biochemical monitoring were good and the few critical topics found in this preliminary study may be addressed with an improvement in information about lithium therapy

Poor sleep quality may independently predict suicidal risk in COVID-19 survivors: a 2-year longitudinal study

Objective: Multiple symptoms of psychiatric, neurological, and physical illnesses may be part of Post-COVID conditions and may pose COVID-19 survivors a high suicidal risk. Accordingly, we aimed to study factors contributing to suicidal risk in Post COVID-19 patients. Method: Consecutive patients with post COVID-19 conditions were followed for 2 years at the University Hospital of Ferrara at baseline (T0), 6 (T1), 12 (T2), and 24 (T3) months. Demographics, and clinical data for all patients included: disease severity, hospital length of stay, comorbidity, clinical complications, sleep quality, cognitive complaints, anxiety and stress-related symptoms, depressive symptoms, and suicidal ideation. Results: The final sample included 81 patients with post COVID survivors. The mean age was 64 + 10,6 years, 35,8% were females, 65,4% had medical comorbidities, and 69,1% had WHO severe form of COVID forms. At T0 more than 90% of patients showed poor sleep quality, 59.3% reported moderate/severe depressive symptoms, and 51.% experienced anxiety, 25.9% experienced post-traumatic stress symptoms. At T0 suicidal ideation, interested 6.1% and at T3 it increased to 7.4%. In the regression analysis, suicidal ideation at baseline was best predicted by poor sleep quality (O.R. 1.71, p=0.044) and, after 2 years, suicidal ideation was best predicted by poor sleep quality experienced at baseline (OR 67.3, p=0.001). Conclusions: Poor sleep quality may play as an independent predictor of suicidal risk in post-COVID survivors. Evaluating and targeting sleep disturbances in COVID survivors is important to prevent the consequences of disrupted sleep in mental health

Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPersistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10-8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.Netherlands Organization for Scientific Research NWO Brain & Cognition 433-09-228 European Research Council ERC-ADG-2014-671084 INSOMNIA Netherlands Scientific Organization (NWO) VU University (Amsterdam, the Netherlands) Dutch Brain Foundation Helmholtz Zentrum Munchen - German Federal Ministry of Education and Research state of Bavaria German Migraine & Headache Society (DMKG) Almirall AstraZeneca Berlin Chemie Boehringer Boots Health Care GlaxoSmithKline Janssen Cilag McNeil Pharma MSD Sharp Dohme Pfizer Institute of Epidemiology and Social Medicine at the University of Munster German Ministry of Education and Research (BMBF) German Restless Legs Patient Organisation (RLS Deutsche Restless Legs Vereinigung) Swiss RLS Patient Association (Schweizerische Restless Legs Selbsthilfegruppe

Melatonin and pro-hypnotic effectiveness of the antidepressant Trazodone: A preliminary evaluation in insomniac mood-disorder patients

Objective To preliminary investigate the link between the darkness hormone melatonin (MLT) and the pro-hypnotic effectiveness of the atypical antidepressant Trazodone (TRZ) in a group of mood disorder patients suffering of insomnia. Design and methods The study's design comprised: i) the enrolment of insomniac outpatients, ii) baseline (t0) psychiatric and biochemical examinations; iii) the subsequent patients' introduction into a treatment with TRZ for 3–4 weeks, followed by post-therapy re-evaluations (t1). The MLT function was investigated by t0/t1 ELISA determinations of 6-hydroxy-MLT sulfate (6-OH-MLTs) levels in early-morning urines and HPLC analysis of morning MLT serum amount. Concomitantly, TRZ and its metabolite m-chloro-phenylpiperazine (m-CPP) were measured by HPLC in serum to monitor patients' compliance/metabolism. Results Seventeen insomniac outpatients, displaying mild symptoms of depression/anxiety resistant to antidepressants, completed TRZ therapy (dose:10–20 mg/day, bedtime). Serum TRZ levels (127 ± 57 ng ml− 1, mean ± SD) confirmed patients' compliance, while the anxiogenic metabolite m-CPP resulting almost undetectable. Moreover, the 6-OH-MLTs output was found increased at t1 vs. baseline values (t1: 58.4 ± 45.02 ng ml− 1; t0: 28.6 ± 15.8 ng ml− 1; mean ± SD, P < 0.05) in 9 patients who recovered both insomnia and depression/anxiety (P < 0.01). Unresponsive subjects showed instead no post-therapy 6-OH-MLTs variation (t1: 48.53 ± 50.70 ng ml− 1; t0: 49.80 ± 66.53 ng ml− 1). Morning MLT in serum slightly diminished at t1 without reaching the statistical significance, not allowing therefore to define the patients' outcome. Conclusions This initial investigation encourages to explore MLT networks as possible correlates of TRZ pro-hypnotic responses

Clinical usefulness of dual orexin receptor antagonism beyond insomnia: Neurological and psychiatric comorbidities

Orexin is a neurotransmitter produced by a small group of hypothalamic neurons. Besides its well-known role in the regulation of the sleep-wake cycle, the orexin system was shown to be relevant in several physiological functions including cognition, mood and emotion modulation, and energy homeostasis. Indeed, the implication of orexin neurotransmission in neurological and psychiatric diseases has been hypothesized via a direct effect exerted by the projections of orexin neurons to several brain areas, and via an indirect effect through orexin-mediated modulation of sleep and wake. Along with the growing evidence concerning the use of dual orexin receptor antagonists (DORAs) in the treatment of insomnia, studies assessing their efficacy in insomnia comorbid with psychiatric and neurological diseases have been set in order to investigate the potential impact of DORAs on both sleep-related symptoms and disease-specific manifestations. This narrative review aimed at summarizing the current evidence on the use of DORAs in neurological and psychiatric conditions comorbid with insomnia, also discussing the possible implication of modulating the orexin system for improving the burden of symptoms and the pathological mechanisms of these disorders. Target searches were performed on PubMed/MEDLINE and Scopus databases and ongoing studies registered on Clinicaltrials.gov were reviewed. Despite some contradictory findings, preclinical studies seemingly support the possible beneficial role of orexin antagonism in the management of the most common neurological and psychiatric diseases with sleep-related comorbidities. However, clinical research is still limited and further studies are needed for corroborating these promising preliminary results

Suicide risk in medically ill inpatients referred to consultation-liaison psychiatric services: A multicenter study

Background: The aim of this multicenter study was to investigate the suicide risk in medically ill patients admitted to six Italian hospitals for whom a consultation-liaison intervention was requested. Methods: Participants completed socio-demographic and clinical report forms and the Brief Illness Perception Questionnaire. Suicidality was assessed using the P4 screener that investigates the presence of Past suicide attempts, Plans to commit a suicide, Probability of completing suicide, and Preventive factors. Participants were categorized as being at no, low or high suicide risk. Univariate and multivariable associations of categorical and continuous variables with suicide risk were investigated using multinomial logistic regression. Results: Of the 641 inpatients, with mean age 60 years (SD = 16.9) and 49.2 % male, 13.2 % were at high suicidal risk (HR), 7.6 % low risk (LR) and 79.2 % no risk. Contacts with psychiatrists in the previous six months were associated with LR and HR (OR = 2.159 and 2.634, respectively), ongoing benzodiazepine use was associated with a threefold likelihood of LR (OR = 3.005), and the experienced intensity of illness symptoms was associated with LR and HR (OR = 1.257 and OR = 1.248, respectively). CL psychiatrists prescribed appropriate psychotropic drugs and activated liaison interventions and psychological support for the level of suicidal risk. Limitations: The use of self-report measures bears the risk of recall bias. Conclusions: Our findings based on psychiatric consultations in the general hospital underscore the need to include suicide risk in the routine assessment of inpatients referred to CL psychiatric services and to plan an appropriate management of suicidal risk after discharge