The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD ...display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (
= 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPI
. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95%
59.2-74.6) for 10-fold cross-validation and 61.9% (95%
52.0-71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.
Abstract
Former prospective studies showed that the occurrence of relapse in Major Depressive Disorder (MDD) is associated with volume loss in the insula, hippocampus and dorsolateral prefrontal ...cortex (DLPFC). However, these studies were confounded by the patient’s lifetime disease history, as the number of previous episodes predict future recurrence. In order to analyze neural correlates of recurrence irrespective of prior disease course, this study prospectively examined changes in brain structure in patients with first-episode depression (FED) over 2 years.
N
= 63 FED patients and
n
= 63 healthy controls (HC) underwent structural magnetic resonance imaging at baseline and after 2 years. According to their disease course during the follow-up interval, patients were grouped into
n
= 21 FED patients with recurrence (FEDrec) during follow-up and
n
= 42 FED patients with stable remission (FEDrem). Gray matter volume changes were analysed using group by time interaction analyses of covariance for the DLPFC, hippocampus and insula. Significant group by time interactions in the DLPFC and insula emerged. Pairwise comparisons showed that FEDrec had greater volume decline in the DLPFC and insula from baseline to follow-up compared with FEDrem and HC. No group by time interactions in the hippocampus were found. Cross-sectional analyses at baseline and follow-up revealed no differences between groups. This longitudinal study provides evidence for neural alterations in the DLPFC and insula related to a detrimental course in MDD. These effects of recurrence are already detectable at initial stages of MDD and seem to occur without any prior disease history, emphasizing the importance of early interventions preventing depressive recurrence.
Background
Bipolar disorders (BD) belong to the most severe mental disorders, characterized by an early onset and recurrent, severe episodes or a chronic course with poor psychosocial functioning in ...a proportion of patients. Many patients with BD experience substantial symptomatology months or even years before full BD manifestation. Adequate diagnosis and treatment is often delayed, which is associated with a worse outcome. This study aims to prospectively evaluate and improve early recognition and intervention strategies for persons at-risk for BD.
Methods
Early-BipoLife is a prospective-longitudinal cohort study of 1419 participants (aged 15–35 years) with at least five waves of assessment over a period of at least 2 years (baseline, 6, 12, 18 and 24 months). A research consortium of ten university and teaching hospitals across Germany conducts this study. The following risk groups (RGs) were recruited: RG I: help-seeking youth and young adults consulting early recognition centres/facilities presenting ≥ 1 of the proposed risk factors for BD, RG II: in-/outpatients with unipolar depressive syndrome, and RG III: in-/outpatients with attention-deficit/hyperactivity disorder (ADHD). The reference cohort was selected from the German representative IMAGEN cohort. Over the study period, the natural course of risk and resilience factors, early symptoms of BD and changes of symptom severity (including conversion to manifest BD) are observed. Psychometric properties of recently developed, structured instruments on potential risk factors for conversion to BD and subsyndromal symptomatology (Bipolar Prodrome Symptom Scale, Bipolar at-risk criteria, EPI
bipolar
) and biomarkers that potentially improve prediction are investigated. Moreover, actual treatment recommendations are monitored in the participating specialized services and compared to recently postulated clinical categorization and treatment guidance in the field of early BD.
Discussion
Findings from this study will contribute to an improved knowledge about the natural course of BD, from the onset of first noticeable symptoms (precursors) to fully developed BD, and about mechanisms of conversion from subthreshold to manifest BD. Moreover, these generated data will provide information for the development of evidence-based guidelines for early-targeted detection and preventive intervention for people at risk for BD.
•Stressful life events in adulthood are negatively associated with grey matter volume in the medial orbitofrontal cortex.•This association was present for both, positive and negative, life ...events.•Early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.
An interplay of early environmental and genetic risk factors with recent stressful life events (SLEs) in adulthood increases the risk for adverse mental health outcomes. The interaction of early risk and current SLEs on brain structure has hardly been investigated.
Whole brain voxel-based morphometry analysis was performed in N = 786 (64.6% female, mean age = 33.39) healthy subjects to identify correlations of brain clusters with commonplace recent SLEs. Genetic and early environmental risk factors, operationalized as those for severe psychopathology (i.e., polygenic scores for neuroticism, childhood maltreatment, urban upbringing and paternal age) were assessed as modulators of the impact of SLEs on the brain.
SLEs were negatively correlated with grey matter volume in the left medial orbitofrontal cortex (mOFC, FWE p = 0.003). This association was present for both, positive and negative, life events. Cognitive-emotional variables, i.e., neuroticism, perceived stress, trait anxiety, intelligence, and current depressive symptoms did not account for the SLE-mOFC association. Further, genetic and environmental risk factors were not correlated with grey matter volume in the left mOFC cluster and did not affect the association between SLEs and left mOFC grey matter volume.
The orbitofrontal cortex has been implicated in stress-related psychopathology, particularly major depression in previous studies. We find that SLEs are associated with this area. Important early life risk factors do not interact with current SLEs on brain morphology in healthy subjects.
We found antibodies to leptospires in 25 (18%) of 141 wild boars from Berlin (95% confidence interval 12-25). Seropositivity was associated with chronic interstitial nephritis (odds ratio 10.5; ...p=0.01), and leptospires were detected in kidney tissues. Wild boars represent a potential source for human leptospirosis in urban environments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The sensitivity of diffusion tensor imaging (DTI) for detecting microstructural white matter alterations has motivated the application of voxel-based statistics (VBS) to fractional anisotropy (FA) ...images (FA-VBS). However, detected group differences may depend on the spatial registration method used. The objective of this study was to investigate the influence of spatial registration on detecting cerebral asymmetries in FA-VBS analyses with reference to data obtained using Tract-Based Spatial Statistics (TBSS). In the first part of this study we performed FA-VBS analyses using three single-contrast and one multi-contrast registration: (i) whole-brain registration based on T2 contrast, (ii) whole-brain registration based on FA contrast, (iii) individual-hemisphere registration based on FA contrast, and (iv) a combination of (i) and (iii). We then compared the FA-VBS results with those obtained from TBSS. We found that the FA-VBS results depended strongly on the employed registration approach, with the best correspondence between FA-VBS and TBSS results when approach (iv), the "multi-contrast individual-hemisphere" method was employed. In the second part of the study, we investigated the spatial distribution of residual misregistration for each registration approach and the effect on FA-VBS results. For the FA-VBS analyses using the three single-contrast registration methods, we identified FA asymmetries that were (a) located in regions prone to misregistrations, (b) not detected by TBSS, and (c) specific to the applied registration approach. These asymmetries were considered candidates for apparent FA asymmetries due to systematic misregistrations associated with the FA-VBS approach. Finally, we demonstrated that the "multi-contrast individual-hemisphere" approach showed the least residual spatial misregistrations and thus might be most appropriate for cerebral FA-VBS analyses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
The stereotypic and oversimplified relationship between female sex hormones and
undesirable behavior dates to the earliest days of human society, as already the
ancient Greek word for the ...uterus, “hystera” indicated an
aversive connection. Remaining and evolving throughout the centuries,
transcending across cultures and various aspects of everyday life, its
perception was only recently reframed. Contemporarily, the complex interaction
of hormonal phases (i. e., the menstrual cycle), hormonal medication
(i. e., oral contraceptives), women’s psychological well-being,
and behavior is the subject of multifaceted and more reflected discussions. A
driving force of this ongoing paradigm shift was the introduction of this highly
interesting and important topic into the realm of scientific research. This
refers to neuroscientific research as it enables a multimodal approach combining
aspects of physiology, medicine, and psychology. Here a growing body of
literature points towards significant alterations of both brain function, such
as lateralization of cognitive functions, and structure, such as gray matter
concentrations, due to fluctuations and changes in hormonal levels. This
especially concerns female sex hormones. However, the more research is conducted
within this field, the less reliable these observations and derived insights
appear. This may be due to two particular factors: measurement inconsistencies
and diverse hormonal phases accompanied by interindividual differences. The
first factor refers to the prominent unreliability of one of the primarily
utilized neuroscientific research instruments: functional magnetic resonance
imaging (fMRI). This unreliability is seemingly present in paradigms and
analyses, and their interplay, and is additionally affected by the second
factor. In more detail, hormonal phases and levels further influence
neuroscientific results obtained through fMRI as outcomes vary drastically
across different cycle phases and medication. This resulting vast uncertainty
thus tremendously hinders the further advancement of our understanding of how
female sex hormones might alter brain structure and function and, ultimately,
behavior.
This review summarizes parts of the current state of research and outlines the
essential requirements to further investigate and understand the female
brain’s underlying physiological and anatomical features.
Emotional instability, difficulties in social adjustment, and disinhibited behavior are the most common symptoms of the psychiatric comorbidities in juvenile myoclonic epilepsy (JME). This ...psychopathology has been associated with dysfunctions of mesial-frontal brain circuits. The present work is a first direct test of this link and adapted a paradigm for probing frontal circuits during empathy for pain. Neural and psychophysiological parameters of pain empathy were assessed by combining functional magnetic resonance imaging (fMRI) with simultaneous pupillometry in 15 JME patients and 15 matched healthy controls. In JME patients, we observed reduced neural activation of the anterior cingulate cortex (ACC), the anterior insula (AI), and the ventrolateral prefrontal cortex (VLPFC). This modulation was paralleled by reduced pupil dilation during empathy for pain in patients. At the same time, pupil dilation was positively related to neural activity of the ACC, AI, and VLPFC. In JME patients, the ACC additionally showed reduced functional connectivity with the primary and secondary somatosensory cortex, areas fundamentally implicated in processing the somatic cause of another's pain. Our results provide first evidence that alterations of mesial-frontal circuits directly affect psychosocial functioning in JME patients and draw a link of pupil dynamics with brain activity during emotional processing. The findings of reduced pain empathy related activation of the ACC and AI and aberrant functional integration of the ACC with somatosensory cortex areas provide further evidence for this network's role in social behavior and helps explaining the JME psychopathology and patients' difficulties in social adjustment.
Neurogranin (NRGN) is the main postsynaptic protein regulating the availability of calmodulin-Ca(2+) in neurons. NRGN is expressed exclusively in the brain, particularly in dendritic spines and has ...been implicated in spatial learning and hippocampal plasticity. Genetic variation in rs12807809 in the NRGN gene has recently been confirmed to be associated with schizophrenia in a meta-analysis of genome-wide association studies: the T-allele was found to be genome-wide significantly associated with schizophrenia. Cognitive tests and personality questionnaires were administered in a large sample of healthy subjects. Brain activation was measured with functional magnetic resonance imaging (fMRI) during an episodic memory encoding and retrieval task in a subsample. All subjects were genotyped for NRGN rs12807809. There was no effect of genotype on personality or cognitive measures in the large sample. Homozygote carriers of the T-allele showed better performance in the retrieval task during fMRI. After controlling for memory performance, differential brain activation was evident in the anterior cingulate cortex for the encoding and posterior cingulate regions during retrieval. We could demonstrate that rs12807809 of NRGN is associated with differential neural functioning in the anterior and posterior cingulate. These areas are involved in episodic memory processes and have been implicated in the pathophysiology of schizophrenia in structural and functional imaging as well as postmortem studies.
...telemedical support has emerged as a potential surge capability not only for the ongoing pandemic but also for future emergencies.5 In March 2021, the Republican Research Centre for Emergency ...Medicine (RRCEM) in Tashkent, Uzbekistan, connected to a telemedical ‘hub’ at the university hospital Charité in Berlin, Germany, to strengthen critical care capacity for patients with severe cases of COVID-19 in Tashkent. Maintaining stable bandwidth and network speed can be challenging in rural areas and must be secured before implementing telemedicine. appropriate hardware and software are other critical components. Telemedicine hardware pieces must be mobile and easy to operate in a clinical setting. the software must be well integrated with the existing and future platforms, not interrupting the workflow, and secure future interoperability as the number of telemedical programmes using electronic medical record systems grows. governments, particularly in low and middle income countries (LMICs), must account for the license and maintenance fees to make telemedicine sustainable. 2. Competing interests CS reports grants from BMG/RKI, during the conduct of the study; grants from Deutsche Forschungsgemeinschaft/ German Research Society, grants from DeutschesZentrum für Luft- und Raumfahrt e. V. (DLR)/‘German Aerospace Center, grants from Einstein Stiftung Berlin/ Einstein Foundation Berlin, grants from Gemeinsamer Bundesausschuss/Federal Joint Committee (G-BA), grants from lnneruniversitäre Forschungsförderung/ Inner University, grants from Projektträger im DLR/Project Management Agency, grants from Stifterverband/ Non-Profit Society Promoting Science and Education, grants from European Society of Anaesthesiology and Intensive Care, grants from Baxter Deutschland, grants from Cytosorbents Europe, grants from Edwards Lifesciences Germany, grants from Fresenius Medical Care, grants from Grünenthal, grants from Masimo Europe, grants from Pfizer Pharma PFE, personal fees from Georg Thieme Verlag, grants from Dr F. Köhler Chemie, grants from Sintetica, grants from Stifterverband für die deutsche Wissenschaft e.V./Philips, grants from Stiftung Charite, grants from AGUETTANT Deutschland, grants from AbbVie Deutschland In addition, CS has a patent 10 2014 215 211.9 licensed, a patent 10 2018 114 364.8 licensed, a patent 10 2018 110 275.5 licensed, a patent 50 2015 010 534.8 licensed, a patent 50 2015 010 347.7 licensed, and a patent 10 2014 215 212.7 licensed.BW reports grants from BMG/RKI, during the conduct of the study; consulting fees from Orion Pharma; honoraria for presentations from Dr F. Köhler Chemie and BARMER Insurance; support for attending meetings from Intouch Health, USA; position as a Committee Chair and Executive Committee Member for ESCIM.
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