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Schizotypy is a putative risk phenotype for psychosis liability, but the overlap of its genetic architecture with schizophrenia is poorly understood.
We tested the hypothesis that dimensions of schizotypy (assessed with the SPQ-B) are associated with a polygenic risk score (PRS) for schizophrenia in a sample of 623 psychiatrically healthy, non-clinical subjects from the FOR2107 multi-centre study and a second sample of 1133 blood donors.
We did not find correlations of schizophrenia PRS with either overall SPQ or specific dimension scores, nor with adjusted schizotypy scores derived from the SPQ (addressing inter-scale variance). Also, PRS for affective disorders (bipolar disorder and major depression) were not significantly associated with schizotypy.
This important negative finding demonstrates that despite the hypothesised continuum of schizotypy and schizophrenia, schizotypy might share less genetic risk with schizophrenia than previously assumed (and possibly less compared to psychotic-like experiences).
Serotonergic neurotransmission plays a key role in seasonal changes of mood and behaviour. Higher serotonin transporter availability in healthy human subjects in times of lesser light has been reported in recent studies. Furthermore, seasonal alterations of postsynaptic serotonin-1A receptors have been suggested by a recent animal study. Following that, this study aimed at identifying seasonal alterations of serotonin-1A receptor binding in the living human brain.
Thirty-six healthy, drug-naïve subjects were investigated using PET and the specific tracer [carbonyl-11C]WAY-100635. Regional serotonin-1A receptor binding (5-HT1A BPND) was related to the individual exposure to global radiation. Furthermore, the subjects were divided into two groups depending on individual exposure to global radiation, and the group differences in regional 5-HT1A BPND were determined.
Correlation analysis controlled for age and gender revealed highly significant positive correlations between regional postsynaptic 5-HT1A BPND and global radiation accumulated for 5 days (r=.32 to .48, p=.030 to .002). Highly significant differences in 5-HT1A BPND binding between subjects with low compared to high exposure to global radiation were revealed (T=-2.63 to -3.77, p .013 to .001). 20% to 30% lower 5-HT1A BPND was found in the subject group exposed to lower amount of global radiation.
Seasonal factors such as exposure to global radiation influence postsynaptic serotonin-1A receptor binding in various brain regions in healthy human subjects. In combination with seasonal alterations in serotonin turnover and 5-HTT availability revealed in recent studies, our results provide an essential contribution of molecular mechanisms in seasonal changes of human serotonergic neurotransmission.
Regional alterations of serotonergic neurotransmission and functional activation in the amygdalar region of patients with major depression are underpinning its important role in affective disorders. In this study we used fMRI and PET to describe functional and molecular alterations associtated with an astrocytoma in the left amygdalar region in a patient with organic depressive disorder compared to control subjects.
The serotonin-1A (5-HT1A) receptor binding (BPND) was quantified with PET (30 frames, 90 min, 4.4 mm FWHM) in 36 subjects using the radioligand [carbonyl-11C]WAY-100635, and a reference tissue model (MRTM2). In fMRI (3T, EPI inplane resolution 1.6*2.7 mm, 10 AC-PC orientated slices, ST = 3 mm, TE/TR = 31/1000 ms), 32 participants performed emotion discrimination and sensorimotor control tasks. Statistical analysis with SPM5 and unpaired t-tests were performed on molecular and functional data separately.
The astrocytoma was delineated in the serotonin-1A receptor distribution showing (p < 0.01, uncorrected) regional BPND decrease. The ipsilateral thalamus and bilateral habenula regions displayed (p < 0.001; uncorrected) BPND increase. The fMRI data showed significantly (p < 0.05; uncorrected) reduced activation in the affected amygdalar region, ipsilateral fusiform gyrus, bilateral orbitofrontal cortex and temporal regions and increased activation in the contralateral temporal pole.
Lower serotonin-1A receptor binding in the left amydala region reflects the glial provenance of the tumor. The increased receptor binding in the habenulae might be associated with altered monoaminergic neurotransmission and depressive symptoms according to the influence of the habenulae on monoaminergic nuclei. The functional data demonstrate neuroplastic changes beyond affected areas and might indicate compensatory mechanisms.
Based on evidences in molecular neuroimaging, postmortem and genetic studies, impaired serotonergic neurotransmission has been implicated with affective disorders. Moreover, a growing number of evidences showed strong interrelations within the serotonergic system suggesting a common mechanism in the modulation of receptor and transporter densities.
Here we directly investigated the regional expression of the 5-HT1A, 5-HT2A and 5-HTT using PET and the three highly selective and specific radioligands [carbonyl-11C]WAY-100635, [18F]Altanserin and [11C]DASB in healthy subjects.
A total of 55 healthy subjects (5-HT1A: 36 subjects, 18 males, age = 26.0 ± 4.9; 5-HT2A: 19 subjects, 11 males, age = 28.2 ± 5.9; 5-HTT: 8 males, age = 28.12 ± 3.6) were included in this study. Binding potential (BPND) values were quantified according to the AAL parcellation scheme.
BPND values averaged over both hemispheres ranged from 0.40–6.35 for the 5-HT1A receptor; 0.01–2.01 for the 5-HT2A receptor and 0.09–2.05 for the 5-HTT, respectively. There was a specific topological pattern according to the ratio between the 5-HT1A, 5-HT2A receptors and 5-HTT (“fingerprints”).
Such information can be essential for detecting potential local alterations in the ratio between different binding proteins on a network level in pathological conditions.
Moreover, these data might provide further insight in area-specific effects of frequently prescribed selective serotonin re-uptake inhibitors (SSRI):
1) due to the distinct local receptor and transporter availability;
2) SSRI application alters the postsynaptic receptor expression and thus;
3) leads to a modified interaction of inhibitory and exhibitory receptors.
Alterations of the serotonin-1A receptor (5-HT1A) and the hypothalamic-pituitary-adrenal (HPA) axis have been reported in depression and anxiety disorders. We previously showed a strong negative correlation between cortisol plasma levels and 5-HT1A receptor binding potential (BP) in patients with social anxiety disorder but not in healthy controls using PET .
To investigate the relationship of cortisol and the 5-HT1A BP in postmenopausal women, a population that is at increased risk of suffering from depressive symptoms.
Subjects: 19 postmenopausal women, aged 55.26 ± 4.98, medication free, no current substance abuse or hormone replacement therapy.
Dynamic measurements (50 frames, 90 min) were performed using the radioligand [carbonyl-11C]WAY100635 and a GE-Advance scanner. PET data were normalized to a ligand-specific template . Regions-of-interest (ROI) were defined as given in . TACs within ROIs were averaged and the 5-HT1A receptor BP was quantified using Logan-plot and PMOD 3.1. Measurement of total cortisol plasma levels was done using electrochemoluminescence.
We found negative correlations between cortisol and 5-HT1A BP in the midbrain (Spearman's rs = −0.54, p = 0.02), the median raphe nucleus (rs = −0.47, p = 0.04) and the nucleus accumbens (rs = −0.505, p = 0.03).
In line with our previous findings , the observed negative association between cortisol plasma levels and 5-HT1A BP might reflect an increased vulnerability for mood disorders in postmenopausal women.
The subgenual part of the anterior cingulate cortex (sgACC) has been frequently reported to be structurally and cytoarchitectually changed in major depressive disorder (MDD) and is also a promising target in deep brain stimulation in treatment-resistant MDD. Furthermore, substantial evidence demonstrates a high density of serotonin-1A (5-HT1A) receptors in the sgACC, a key area involved in emotional processing.
Here, we investigated the relationship between the 5-HT1A receptor in the sgACC and changes in regional grey matter volume with voxel-based morphometry.
PET ([carbonyl-11C]WAY-100635) was used to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance images from 32 healthy subjects (mean 26.68 ± 5.1 years; 17 women). Regression analysis was performed in SPM8 (p < .001 uncorr.) using sgACC 5-HT1A BPND as regressor, controlling for sex, age and total grey matter volume (GMV).
5-HT1A BPND in the sgACC was positively associated with regional GMV in the medial temporal gyri (T=4.37) and nucleus accumbens bilaterally (T = 4.19). Furthermore, sgACC 5-HT1A binding was negatively correlated with GMV within the inferior temporal gyri (T = 5.22) and putamen bilaterally (T = 5.12).
Our findings demonstrate structural relationships between sgACC 5-HT1A receptor binding and grey matter volume in the ventral striatum as well as in temporal regions, which both exhibit close neuronal connections with the sgACC. Moreover, the GMV of the ventral striatum has been reported to be decreased in patients with MDD. Conclusively, our results underpin the role of serotonergic neuronal transmission in cytoarchitectural processes within regions involved in the modulation of mood.
Dysfunctional neuroplasticity contributes to the pathogenesis of Alzheimer's disease, schizophrenia and depression. However, the underlying molecular mechanisms are not fully understood. Previous studies report neuromodulatory properties of the serotonin-1A (5-HT1A) receptor, which is also altered in these disorders. This suggests 5-HT1A mediated neuroplasticity as potential pathogenic factor.
The aim of this study was to demonstrate 5-HT1A mediated neuroplasticity in vivo.
We used positron emission tomography to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance imaging in 35 healthy subjects (mean 26.6 ±6.8 years; 17 women). Voxel-wise regression analysis was performed with gray matter volume (GMV) as dependent and 5-HT1A BPND as independent variable. Additionally, regression analysis was calculated with whole brain GMV as dependent variable and 5-HT1A BPND of the dorsal raphe nucleus (DRN) as independent variable. Control variables were age, sex and total GMV, respectively.
5-HT1A receptor density predicted GMV of the hippocampus, medial temporal cortex, inferior temporal cortex, medial occipital cortex and the pericalcarine region in each hemisphere (p < 0.05 false discovery rate corrected, R2: 0.308–0.503). These associations were independent from local numbers of neurons. Furthermore, 5−HT1A receptor levels in the DRN predicted GMV of the anterior cingulate cortex (p = 0.001, R2=0.656, uncorrected).
These results demonstrate 5-HT1A receptor mediated morphogenetic mechanisms in healthy human subjects' brains, which occur not only locally but also at the macro-network level. Finally, morphogenetic signaling investigated with multimodal neuroimaging could contribute to better understanding and diagnostic identification of gray matter loss in neuropsychiatric disorders.
The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, indicating similar asymmetries in associated neurotransmitter systems.
To investigate a potential brain asymmetry of the serotonin transporter (SERT) distribution using Positron Emission Tomography (PET).
As brain asymmetries differ between sexes, we aimed to compare serotonin transporter asymmetry between females, males and male-to-female transsexuals whose brains are considered to be partly feminized.
36 subjects aged 19-54 years (9 female controls, 13 male controls and 14 male-to-female transsexuals) were measured with PET and [11C]DASB. Whole-brain voxel-wise SERT binding potential (BPND) maps were computed using a tracer-specific symmetric template. Statistics comprised repeated measures ANOVA with group as the between subjects factor, voxel-wise SERT asymmetry as repeated factor and group*asymmetry as interaction term.
SERT binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus (p< 0.05 FDRcorrected). Further, male controls showed a rightward asymmetry in the midcingulate cortex (p>0.05 FDR-corrected) which was absent in females and male-to-female transsexuals.
Our data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in male-to-female transsexuals may be attributed to an absence of brain masculinization in this region.
Vietnamese migrants under the influence of migration-related stressors (MRS) represent a vulnerable group within the mental health care system in Germany.
First study examining the relationship between the quantity of experienced MRS and the severity of self-reported symptoms of depression in a Vietnamese outpatient-sample.
137 first-generation Vietnamese migrants diagnosed with depression were asked to complete the BDI-II and 24 questions about stressful experiences related to the migration process. Linear regression models was performed to examine the influence of the MRS-quantity on BDI-II total score and on BDI-II subscales (Buckley et al., 2001).
A higher number of experienced MRS was found to be related to a higher BDI-II total score, as well as to a higher score on the cognitive subscale in particular. Regarding the cognitive depression-dimension the BDI-II items pessimism, past failure, guilt feelings, punishment feelings and suicidal thoughts were positively related to the MRS-quantity.
Discussion and conclusion
A dose-response-relationship was found, with a higher number of MRS being related to a higher severity level of self-reported depressiveness as well as to a higher level of cognitive depression-symptoms in particular. The increase in suicidal ideations in the light of MRS-exposure is in line with findings from other migrant populations. Therapeutic interventions may focus (more) on depressive cognitions as a result of recurring MRS-experiences. Special attention should be placed on suicidal thoughts being boosted by MRS.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
A multidisciplinary mineralogical, geochemical and biomarker study of Indus Fan sediments cored during International Ocean Discovery Program (IODP) Expedition 355 to the Laxmi Basin was carried out to define the different compositional signatures of sand, silt and clay. Upper Pliocene – lower Pleistocene turbidites from sites U1456 and U1457 were selected as the best candidates for this study. The integrated dataset presented here was obtained by coupling traditional and innovative bulk-sediment and single-mineral techniques on the same samples. Turbiditic deposits mostly consist of medium to fine silt, including rich and diverse heavy-mineral assemblages. Such a fine grain size forced us to push the limits of high-resolution quantitative heavy-mineral analysis down to as low as 5 μm. Heavy-mineral analysis allowed us to establish a Himalayan origin of the detritus in the studied turbidites. Heavy-mineral concentrations are higher in channel-fill than in overbank deposits. Mineralogical and geochemical data concur in revealing that fast-settling ultradense minerals such as zircon are preferentially concentrated in channel-fill deposits, whereas the top of overbank deposits are notably enriched with slow-settling platy phyllosilicates. Biomarker analysis represents a most suitable complementary technique that is able to investigate the provenance signature of the finer sediment fraction, largely consisting of clay. This technique allowed us to identify a largely terrigenous origin of organic matter at Site U1456 and an open marine origin at Site U1457. The latter site lies closer to the Laxmi Ridge, where thermal maturity increases with depth to reach the early oil window (127°C at c. 320 m below the seafloor).
Background: Continuous electroencephalographic (cEEG) monitoring is essential to diagnosing non-convulsive seizures (NCS), reported to occur in 7-46% of at-risk critically ill patients. However, cEEG is labour-intensive, and given scarcity of resources at most centres cEEG is feasible in only selected patients. We aim to evaluate the clinical utility of cEEG at our centre in order to optimize further cEEG allocation among critically ill patients. Methods: Using a clinical database, we identified critically ill children who underwent cEEG monitoring in 2016, 2017 and 2018. We abstracted underlying diagnoses, indication for cEEG monitoring, cEEG findings, and associated changes in management. Results: Over this three year period, 928 cEEGs were performed. Among the 100 studies analyzed to date, primary indications for monitoring were characterization of events of unclear etiology (32%), diagnosis of NCS (30%), and monitoring of therapy for seizures (17%). Seizures were captured in 31% of patients (22% subclinical only, 5% electroclinical only, 4% both), which resulted in a treatment change in 90% of cases. Non-epileptic events were captured in 26% of patients. Conclusions: cEEG yielded clinically meaningful information in 57% of cases, frequently resulting in management changes. Subgroup analyses by cEEG indication and ICU location will be presented.
OBJECTIVES/SPECIFIC AIMS: To evaluate the NIH-sponsored Best Practices for Social and Behavioral Research e-learning course. METHODS/STUDY POPULATION: Four universities partnered in a pilot study to evaluate this new course. Outcomes from 294 participants completing the course included efficient progress through the training, perceived relevance of the course to current work, level of engagement with the course material, intent to work differently as a result of the course, and downloading digital resources. RESULTS/ANTICIPATED RESULTS: Participants rated the course as relevant and engaging (6.4 and 5.8 on a 7-point Likert scale) and 96% of respondents said they would recommend the course to colleagues. Qualitative analysis of participant testimonials suggested that most respondents had a readiness to change in the way they worked as a result of the course. Overall, results suggest participants completed the course efficiently, perceived outcomes positively and worked differently after the training. DISCUSSION/SIGNIFICANCE OF IMPACT: These results will inform new guidelines for future participants (e.g., average time to complete, expectations for knowledge checks in the training). Future studies should include larger samples and closer coordination and communication between study sites.
Background: Registered EEG technologists (RETs) are trained in both the technical aspects of EEG and in preliminary EEG interpretation. However, there is little research evaluating the accuracy of EEG interpretation by RETs. Methods: Retrospective study of consecutive routine EEG recordings performed at SickKids Hospital. Preliminary reports by RETs and final reports by neurophysiologists were compared in 5 domains: background activity, focal abnormalities, ictal and inter-ictal epileptiform discharges and summary. Results: 500 EEG recordings were analyzed. Sensitivity and specificity of RET reports was high for the assessment of background (85%, 93%), focal slowing (84%, 93%) and inter-ictal epileptiform discharges (92%, 90%). RET reports identified ictal EEG patterns in 32 cases vs. 29 cases identified by neurophysiologists. RET reports were 100% accurate for noting no EEG change for all of 11 cases with non-epileptic events. Conclusions: Preliminary EEG reports by RETs were sensitive and specific for all EEG domains analyzed. In the majority of cases, the preliminary interpretation made by the RET was concordant with the final report of the neurophysiologist. Given these findings, RETs may be able to participate in the screening of routine EEG recordings in order to enhance the productivity of busy EEG laboratories.
Background: Flow cytometry in the cerebrospinal fluid (CSF) is used as an adjunct to cytology to increase the sensitivity of detecting central nervous system (CNS) lymphoma. We aim to evaluate CSF flow cytometry as a diagnostic tool for lymphoma in patients presenting with undifferentiated neurologic symptoms. Methods: We retrospectively reviewed all CSF flow cytometry samples sent in the Calgary region from 2012-2015. Clinical data, laboratory investigations, radiologic imaging studies, and pathological data were analyzed. Clinical review extended to 2 years post CSF flow cytometric testing. Results: The number of samples of CSF flow cytometry that were positive for a hematological malignancy was 43/763 (5.6%). The overall sensitivity of the test was 72.9%. A positive result was more likely to occur in patients with a prior history of a hematological malignancy or abnormal enhancement on MRI (p<0.0001). In fact, CSF flow cytometry was negative in all patients who did not have a previous hematological malignancy or abnormal enhancement on MRI (n = 247). Conclusions: CSF flow cytometry has very limited role in the screening for primary CNS lymphoma, unless a strictly endorsed testing algorithm is applied. It is, however, an invaluable tool in assessing CNS involvement in patients with previous diagnosis of hematolymphoid malignancy.
The Best Practices in Social and Behavioral Research Course was developed to provide instruction on good clinical practice for social and behavioral trials. This study evaluated the new course.
Participants across 4 universities took the course (n=294) and were sent surveys following course completion and 2 months later. Outcomes included relevance, how engaging the course was, and working differently because of the course. Open-ended questions were posed to understand how work was impacted.
Participants rated the course as relevant and engaging (6.4 and 5.8/7 points) and reported working differently (4.7/7 points). Participants with less experience in social and behavioral trials were most likely to report working differently 2 months later.
The course was perceived as relevant and engaging. Participants described actions taken to improve rigor in implementing trials. Future studies with a larger sample and additional participating sites are recommended.
Simulation of the water balance in cropping systems is an essential tool, not only to monitor water status and determine drought but also to find ways in which soil water and irrigation water can be used more efficiently. However, besides the requirement that models are physically correct, the spatial representativeness of input data and, in particular, accurate precipitation data remain a challenge. In recent years, satellite-based soil moisture products have become an important data source for soil wetness information at various spatial-temporal scales. Four different study areas in the Czech Republic and Austria were selected representing Central European soil and climatic conditions. The performance of soil water content outputs from two different crop-water balance models and the Metop Advanced SCATterometer (ASCAT) soil moisture product was tested with field measurements from 2007 to 2011. The model output for soil water content shows that the crop model Decision Support System for Agrotechnology Transfer performs well during dry periods (<30% plant available soil moisture (ASM), whereas the soil water-balance model SoilClim presents the best results in humid months (>60% ASM). Moreover, the model performance is best in the early growing season and decreases later in the season due to biases in simulated crop-related above-ground biomass compared with the relatively stable grass canopy of the measurement sites. The Metop ASCAT soil moisture product, which presents a spatial average of soil surface moisture, shows the best performance under medium soil wetness conditions (30–50% ASM), which is related to low variation in precipitation frequency and under conditions of low-surface biomass (early vegetation season).