Limited evidence of autocorrelation signaling upcoming affective episodes: a 12-month e-diary study in patients with bipolar disorder.

BACKGROUND: Increased autocorrelation (AR) of system-specific measures has been suggested as a predictor for critical transitions in complex systems. Increased AR of mood scores has been reported to anticipate depressive episodes in major depressive disorder, while other studies found AR increases to be associated with depressive episodes themselves. Data on AR in patients with bipolar disorders (BD) is limited and inconclusive. METHODS: Patients with BD reported their current mood via daily e-diaries for 12 months. Current affective status (euthymic, prodromal, depressed, (hypo)manic) was assessed in 26 bi-weekly expert interviews. Exploratory analyses tested whether self-reported current mood and AR of the same item could differentiate between prodromal phases or affective episodes and euthymia. RESULTS: A total of 29 depressive and 20 (hypo)manic episodes were observed in 29 participants with BD. Self-reported current mood was significantly decreased during the two weeks prior to a depressive episode (early prodromal, late prodromal), but not changed prior to manic episodes. The AR was neither a significant predictor for the early or late prodromal phase of depression nor for the early prodromal phase of (hypo)mania. Decreased AR was found in the late prodromal phase of (hypo)mania. Increased AR was mainly found during depressive episodes. CONCLUSIONS: AR changes might not be better at predicting depressive episodes than simple self-report measures on current mood in patients with BD. Increased AR was mostly found during depressive episodes. Potentially, changes in AR might anticipate (hypo)manic episodes.

[Chronobiological aspects of bipolar disorder]. / Chronobiologische Aspekte der bipolaren Störung.

BACKGROUND: Numerous symptoms of bipolar disorder are regulated by the circadian rhythm. Because of this association it is assumed that disruption of the circadian rhythm may be part of the pathomechanism of bipolar disorder. OBJECTIVES: A comparison and subsequent critical discussion of the current data situation on chronobiological aspects of bipolar disorder are presented. METHODS: A narrative literature search was carried out and the main findings are presented in a summarized form. RESULTS: There are a large number of animal and human studies investigating the connection between disorders of the circadian rhythm and bipolar disorder. Especially chronotype, the environmental factor light and sleep disorders seem to be associated with the development of bipolar disorder. CONCLUSIONS: The neurobiology of bipolar disorder shows numerous chronobiological aspects. There is evidence for a direct connection of disruption of the circadian rhythm and development and progression of bipolar disorder; however, at present there is no proof for the specificity of these findings for bipolar disorder. Future studies should consolidate the evidence on the impact of disorders of the circadian rhythm on the pathomechanism of bipolar disorder.

THz microscope for three-dimensional imaging with superconducting Josephson junctions.

Superconducting Josephson junctions have a wide range of applications ranging from quantum computing to voltage standards, and they may also be employed as versatile sensors for high-frequency radiation and magnetic fields. In this work, we present a unique measurement setup utilizing a single Josephson junction on a cantilever for high-resolution spatial measurements of spectroscopically resolved THz and microwave field distributions. This THz microscope can be utilized to measure power and frequency of electromagnetic radiation from ∼1 GHz to 5 THz. It may also be used to measure static magnetic fields and provide topological scans of samples. The samples can be both actively radiating or passively irradiated at either room temperature or cryogenic temperatures. We review the measurement setup of the THz microscope and describe the evaluation of its measurement data to achieve three-dimensional visualizations of the field distributions. The diverse capabilities of this unique tool are demonstrated by its different measurement modes with measurements of field distributions at 20 GHz and 1.4 THz, spectroscopically resolved THz measurements, and magnetic field measurements.

Movement disorders after hypoxic brain injury following cardiac arrest in adults.

BACKGROUND AND PURPOSE: Post-hypoxic movement disorders and chronic post-hypoxic myoclonus are rare complications after cardiac arrest in adults. Our study investigates the clinical spectrum, neuroimaging results, therapy and prognosis of these debilitating post-hypoxic sequelae. METHODS: This retrospective study included 72 patients from the neurological intensive care unit at a university hospital, who were diagnosed with hypoxic-ischaemic encephalopathy after cardiac arrest between January 2007 and September 2018. Clinical records were screened for occurrence of post-hypoxic movement disorders and chronic post-hypoxic myoclonus. Affected patients were further analysed for applied neuroprognostic tests, administered therapy and treatment response, and the outcome of these movement disorders and neurological function. RESULTS: Nineteen out of 72 screened patients exhibited post-hypoxic motor symptoms. Basal ganglia injury was the most likely neuroanatomical correlate of movement disorders as indicated by T1 hyperintensities and hypometabolism of this region in magnetic resonance imaging and positron emission tomography computed tomography. Levomepromazine and intrathecal baclofen showed first promising and mostly prompt responses to control these post-hypoxic movement disorders and even hyperkinetic storms. In contrast, chronic post-hypoxic myoclonus best responded to co-application of clonazepam, levetiracetam and primidone. Remission rates of post-hypoxic movement disorders and chronic post-hypoxic myoclonus were 58% and 50%, respectively. Affected patients seemed to present a rather good recovery of cognitive functions in contrast to the often more severe physical deficits. CONCLUSIONS: Post-hypoxic movement disorders associated with pronounced basal ganglia dysfunction might be efficiently controlled by levomepromazine or intrathecal baclofen. Their occurrence might be an indicator for a more unfavourable, but often not devastating, neurological outcome.

[A review of the update of the German S3-guideline on diagnostics and therapy of bipolar disorders 2019]. / Überblick über Neuerungen der überarbeiteten und aktualisierten Leitlinie zur Diagnostik und Therapie bipolarer Störungen 2019.

Since the first publication of the guideline in 2012, which included critically reviewed evidence up to 2010, several hundred articles with new evidence were published and some topics of the clinical consensus needed to be reconsidered. Therefore, it was urgently necessary to revise the guideline to bring them up to date. In this article important revisions and updates are presented and the chances and limitations of the development of the guidelines and their implementation are discussed.

[Ambulatory monitoring and digital phenotyping in the diagnostics and treatment of bipolar disorders]. / Ambulantes Monitoring und digitale Phänotypisierung in Diagnostik und Therapie bipolarer Erkrankungen.

BACKGROUND: Reliable and valid diagnostics and treatment of bipolar disorders and affective episodes are subject to extensive, especially methodological limitations in the clinical practice. OBJECTIVE: The use of smartphones and mobile sensor technology for improvement in diagnostics and treatment of bipolar disorders. METHODS: Critical discussion of current research on the use of ambulatory monitoring and digital phenotyping with bipolar disorders. RESULTS: In many studies the observation periods were too short and the sensors applied were too inaccurate to enable reliable and valid detection of behavioral changes in the context of affective episodes. CONCLUSION: The clarification and operationalization of psychopathological constructs to allow for the measurement of objectively observable and ascertainable behavioral changes during depressive and (hypo)manic states are essential for the successful application of modern mobile technologies in the diagnostics and treatment of bipolar disorders.

A systematic review on sleep alterations anticipating the onset of bipolar disorder.

BACKGROUND: Sleep alterations are frequent occurrence in Bipolar Disorder (BD), both in acute and interepisodic phases. Sleep alterations have been also described both long before BD onset, as aspecific risk syndromes, or as immediate prodromes of BD onset. The aim of the present study is to systematically review the relationship between sleep alterations anticipating for the full-blown onset of BD, both in general and according to specific polarities of onset. METHODS: A systematic literature research according to PRISMA statement and considering: 1. prospective studies about BD patients' offspring with sleep alterations who later developed BD. 2. prospective studies assessing patients with sleep disorders who later developed BD. 3. retrospective studies on BD patients where sleep alterations before BD onset of the disease were reported. RESULTS: A total of 16 studies were included in this review. Sleep disturbances may frequently appear 1 year before the onset of BD or more, often during childhood or adolescence. A decreased need for sleep may precede the onset of the illness, specially a manic episode, while insomnia appears to anticipate either a manic or a depressive episode. Hypersomnia seems to precede bipolar depressive episodes. CONCLUSIONS: Sleep alterations frequently appear long before the onset of BD, and appear to be related specifically to the polarity of the index episode. The detection and treatment of sleep alterations in special high risk populations may help achieving an earlier detection of the illness.

Subject specificity of the correlation between large-scale structural and functional connectivity.

Structural connectivity (SC), the physical pathways connecting regions in the brain, and functional connectivity (FC), the temporal coactivations, are known to be tightly linked. However, the nature of this relationship is still not understood. In the present study, we examined this relation more closely in six separate human neuroimaging datasets with different acquisition and preprocessing methods. We show that using simple linear associations, the relation between an individual's SC and FC is not subject specific for five of the datasets. Subject specificity of SC-FC fit is achieved only for one of the six datasets, the multimodal Glasser Human Connectome Project (HCP) parcellated dataset. We show that subject specificity of SC-FC correspondence is limited across datasets due to relatively small variability between subjects in SC compared with the larger variability in FC.

Sleep spindles in bipolar disorder - a comparison to healthy control subjects.

OBJECTIVE: Bipolar disorder is a severe mental disorder for which currently no reliable biomarkers exist. It has been shown that patients with schizophrenia but not with unipolar depression have a reduced density of fast sleep spindles during N2 sleep. The aim of this study was to assess fast sleep spindle density in euthymic patients with bipolar disorder. METHODS: Patients with bipolar disorder (n = 24) and healthy control subjects (n = 25) were assessed using all-night polysomnography. Sleep spindles within stage N2 sleep were identified by visual inspection and subdivided into fast (>13 Hz) and slow (≤13 Hz) spindles. All spindles were subsequently characterised by density, frequency, amplitude, duration and coherence. RESULTS: Euthymic patients with bipolar disorder were found to have a reduced density and a lower mean frequency of fast spindles. Slow spindle density and frequency did not differ between groups. There were no differences regarding amplitude, duration or coherence. CONCLUSIONS: A reduction in fast spindle density during N2 sleep points towards thalamic dysfunction as a potential neurobiological mechanism of relevance in bipolar disorder. In addition, a reduced sleep spindle density could be interpreted as a common endophenotype shared with schizophrenia but not unipolar depression and may - if replicated - be of utility in early recognition and risk stratification.

Differentiation of Alzheimer's disease based on local and global parameters in personalized Virtual Brain models.

Alzheimer's disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, "The Virtual Brain (TVB)", based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioural spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

[Guideline-adherent psychiatric psychotherapeutic treatment of bipolar disorders : Which resources are needed?] / Leitliniengerechte psychiatrisch-psychotherapeutische Behandlung bei bipolaren Störungen : Welche Ressourcen werden dafür benötigt?

In this article the guideline-adherent psychiatric psychotherapeutic treatment of patients with bipolar disorders is outlined and the required resources are estimated. Based on the core recommendations of the S3 guidelines for diagnostics and treatment of bipolar disorders published in 2012, inpatient treatment needs in hours per week and per patient are determined for both manic and bipolar depressive episodes. The resulting staffing requirements are estimated on this basis. In summary, for guideline-adherent inpatient psychiatric psychotherapeutic treatment the additional needs regarding the physician/psychotherapeutic domain add up to 44 min per patient and week during a manic episode and 88 min for patients with bipolar depression when compared to current psychiatry staffing regulations.

Accuracy of the pacemaker-mediated tachycardia algorithm in Boston Scientific devices.

INTRODUCTION: The incidence of pacemaker-mediated tachycardia (PMT) varies as a function of patient characteristics, device programming and algorithm specificities. We investigated the efficacy of the Boston Scientific algorithm by reviewing PMT episodes in a large device population. METHODS: In this multicenter study, we included 328 patients implanted with a Boston Scientific device: 157 non-dependent patients with RYTHMIQ™ activated (RYTHMIQ group), 76 patients with permanent AV-conduction disorder (AV-block group) and 95 Cardiac Resynchronization Therapy patients (CRT group). For each patient, we reviewed the last 10 remote monitoring-transmitted EGMs diagnosed as PMT. RESULTS: We analyzed 784 PMT episodes across 118 patients. In the RYTHMIQ group, the diagnosis of PMT was correct in most episodes (80%) of which 69% was directly related to the prolongation of the AV-delay associated with the RYTHMIQ algorithm. The usual triggers for PMT were also observed (PVC 16%, PAC 9%). The remainder of the episodes (20%) in RYTHMIQ patients and most episodes of AV-block (66%) and CRT patients (74%) were incorrectly diagnosed as PMT during sinus tachycardia at the maximal tracking rate. The inappropriate intervention of the algorithm during exercise causes non-conducted P-waves, loss of CRT (sustained in six patients) and may have been pro-arrhythmogenic in one patient (induction of ventricular tachycardia). CONCLUSION: Algorithms to minimize ventricular pacing can occasionally have unintended consequences such as PMT. The PMT algorithm in Boston Scientific devices is associated with a high rate of incorrect PMT diagnosis during exercise resulting in inappropriate therapy with non-conducted P-waves, loss of CRT and limited risk of pro-arrhythmic events.

[Effects of fine particulate matter from on bronchial epithelial cells]. / Effets des particules fines sur les cellules épithéliales bronchiques.

INTRODUCTION: Ambient air contains a variety of pollutants including solid particles. Human bronchial epithelial cells (HBEC) play a key role following inhalation of these toxic particles. In a cell culture system of HBEC, we investigated the effects of several fractions of Lyons air-derived particles on cell viability/proliferation and production of the inflammatory mediators IL-8 and TGF-ß. METHODS: Air particles were collected in Lyon (France) by filtration of the air and impaction on filters located on a tapered element oscillating microbalance. Several diameter-based fractions of particles were prepared. HBEC were then exposed to different concentrations of these fractions. RESULTS: HBEC survival was not altered after 48hours of culture in the presence of particles regardless of their diameter and concentration. A dose-dependent inhibitory effect on cell growth was observed for all fractions. The particles caused an increase of both TGF-ß and Il-8 protein levels as a function of their diameters and/or concentrations. CONCLUSION: Air-derived particle fractions exhibit both an inhibitory effect on cell proliferation and a pro-inflammatory activity on HBEC.

Symptom characteristics of depressive episodes prior to the onset of mania or hypomania.

OBJECTIVE: Depressive episodes are typically the initial presentation of bipolar disorder. The evidence as to whether depressive episodes occurring in persons who later convert to bipolar disorder are symptomatically distinct from episodes of unipolar depression remains controversial. As there are crucial differences in the therapeutic management, symptom profiles indicating subsequent bipolar conversion may aid in appropriate treatment. METHOD: A representative community sample of originally N = 3021 adolescents and young adults aged 14-24 years at baseline was assessed up to four times over 10 years. Assessment of symptoms was conducted by clinically trained interviewers using the standardized M-CIDI. Symptom profiles of depressive episodes were compared via logistic regression between subjects that subsequently developed (hypo-)manic episodes (n = 35) or remained unipolar depressive (n = 659). RESULTS: Initial depression amongst prospective converters was characterized by significantly increased suicidality (odds ratio, OR = 2.31), higher rates of feelings of worthlessness and excessive guilt (OR = 2.52), complete loss of pleasure (OR = 2.53) and diurnal variation (OR = 4.30). No differences were found for hyperphagia, hypersomnia and psychomotor alterations. CONCLUSION: Findings suggest that the symptom profile of initial depressive episodes may be useful in the identification of subjects with an elevated risk for the subsequent conversion to bipolar disorder.

[Is there an increased risk for renal tumors during long-term treatment with lithium?]. / Gibt es bei der Lithiumlangzeitbehandlung ein erhöhtes Risiko für Nierentumoren?

Lithium salts are the recommended first-line treatment (gold standard) in national and international treatment guidelines for acute and maintenance treatment of affective disorders, such as bipolar disorders. Lithium has also been shown to have a unique protective effect against suicide in patients suffering from affective disorders. Despite the well-known acute and long-term adverse effects lithium therapy can be safely administered if patients are properly educated and carefully monitored. A recent study from France now shows that patients with severely impaired renal function who had been treated with lithium salts for more than 10 years could have an increased risk for kidney tumors (benign and malignant). This resulted in an adjustment concerning information within the package leaflet by European authorities. The authors of this article reflect the currently available data in order to better understand and handle this new finding and to warn about uncritical reactions including withdrawal of lithium in successfully treated patients. This article provides clinical recommendations to provide further insight relating to the risk of kidney cancer in long-term lithium therapy.

The suicide prevention effect of lithium: more than 20 years of evidence-a narrative review.

The management and treatment of patients with suicidal behavior is one of the most challenging tasks for health-care professionals. Patients with affective disorders are at high risk for suicidal behavior, therefore, should be a target for prevention. Numerous international studies of lithium use have documented anti-suicidal effects since the 1970s. Despite the unambiguous evidence of lithium's anti-suicidal effects and recommendations in national and international guidelines for its use in acute and maintenance therapy of affective disorders, the use of lithium is still underrepresented. The following article provides a comprehensive review of studies investigating the anti-suicidal effect of lithium in patients with affective disorders.

Does lithium reduce acute suicidal ideation and behavior? A protocol for a randomized, placebo-controlled multicenter trial of lithium plus Treatment As Usual (TAU) in patients with suicidal major depressive episode.

BACKGROUND: Lithium has proven suicide preventing effects in the long-term treatment of patients with affective disorders. Clinical evidence from case reports indicate that this effect may occur early on at the beginning of lithium treatment. The impact of lithium treatment on acute suicidal thoughts and/or behavior has not been systematically studied in a controlled trial. The primary objective of this confirmatory study is to determine the association between lithium therapy and acute suicidal ideation and/or suicidal behavior in inpatients with a major depressive episode (MDE, unipolar and bipolar disorder according to DSM IV criteria). The specific aim is to test the hypothesis that lithium plus treatment as usual (TAU), compared to placebo plus TAU, results in a significantly greater decrease in suicidal ideation and/or behavior over 5 weeks in inpatients with MDE. METHODS/DESIGN: We initiated a randomized, placebo-controlled multicenter trial. Patients with the diagnosis of a moderate to severe depressive episode and suicidal thoughts and/or suicidal behavior measured with the Sheehan-Suicidality-Tracking Scale (S-STS) will be randomly allocated to add lithium or placebo to their treatment as usual. Change in the clinician administered S-STS from the initial to the final visit will be the primary outcome. DISCUSSION: There is an urgent need to identify treatments that will acutely decrease suicidal ideation and/or suicidal behavior. The results of this study will demonstrate whether lithium reduces suicidal ideation and behavior within the first 5 weeks of treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02039479.

[Ketamine as antidepressant: the current study situation]. / Ketamin als Antidepressivum : Die aktuelle Studienlage.

The treatment of depressive episodes is characterized by a delay in response of antidepressant medications and high rates of therapeutic failure. In recent years several open and five controlled trials have demonstrated the antidepressant efficacy of ketamine for major depression. In addition a recent study established the utility of nasal ketamine which may render the necessity of intravenous administration obsolete. The current state of evidence is reviewed and discussed.