Neuroplastic effects of a selective serotonin reuptake inhibitor in relearning and retrieval.

Animal studies using selective serotonin reuptake inhibitors (SSRIs) and learning paradigms have demonstrated that serotonin is important for flexibility in executive functions and learning. SSRIs might facilitate relearning through neuroplastic processes and thus exert their clinical effects in psychiatric diseases where cognitive functioning is affected. However, translation of these mechanisms to humans is missing. In this randomized placebo-controlled trial, we assessed functional brain activation during learning and memory retrieval in healthy volunteers performing associative learning tasks aiming to translate facilitated relearning by SSRIs. To this extent, seventy-six participants underwent three MRI scanning sessions: (1) at baseline, (2) after three weeks of daily associative learning and subsequent retrieval (face-matching or Chinese character-noun matching) and (3) after three weeks of relearning under escitalopram (10 mg/day) or placebo. Associative learning and retrieval tasks were performed during each functional MRI (fMRI) session. Statistical modeling was done using a repeated-measures ANOVA, to test for content-by-treatment-by-time interaction effects. During the learning task, a significant substance-by-time interaction was found in the right insula showing a greater deactivation in the SSRI cohort after 21 days of relearning compared to the learning phase. In the retrieval task, there was a significant content-by-time interaction in the left angular gyrus (AG) with an increased activation in face-matching compared to Chinese-character matching for both learning and relearning phases. A further substance-by-time interaction was found in task performance after 21 days of relearning, indicating a greater decrease of performance in the placebo group. Our findings that escitalopram modulate insula activation demonstrates successful translation of relearning as a mechanism of SSRIs in human. Furthermore, we show that the left AG is an active component of correct memory retrieval, which coincides with previous literature. We extend the function of this region by demonstrating its activation is not only stimulus dependent but also time constrained. Finally, we were able to show that escitalopram aids in relearning, irrespective of content.

Novel collophorina-like genera and species from Prunus trees and vineyards in Germany.

Strains with a yeast-like appearance were frequently collected in two surveys on the biodiversity of fungi in Germany, either associated with necroses in wood of Prunus trees in orchards in Saxony, Lower Saxony and Baden-Württemberg or captured in spore traps mounted on grapevine shoots in a vineyard in Rhineland-Palatinate. The morphology of the strains was reminiscent of the genus Collophorina: all strains produced aseptate conidia on integrated conidiogenous cells directly on hyphae, on discrete phialides, adelophialides and by microcyclic conidiation, while in some strains additionally endoconidia or conidia in conidiomata were observed. Blastn searches with the ITS region placed the strains in the Leotiomycetes close to Collophorina spp. Analyses based on morphological and multi-locus sequence data (LSU, ITS, EF-1α, GAPDH) revealed that the 152 isolates from wood of Prunus spp. belong to five species including C. paarla, C. africana and three new species. A further ten isolates from spore traps belonged to seven new species, of which one was isolated from Prunus wood as well. However, a comparison with both LSU and ITS sequence data of these collophorina-like species with reference sequences from further Leotiomycetes revealed the genus Collophorina to be polyphyletic and the strains to pertain to several genera within the Phacidiales. Collophorina paarla and C. euphorbiae are transferred to the newly erected genera Pallidophorina and Ramoconidiophora, respectively. The new genera Capturomyces, Variabilispora and Vexillomyces are erected to accommodate five new species isolated from spore traps. In total nine species were recognised as new to science and described as Collophorina badensis, C. germanica, C. neorubra, Capturomyces funiculosus, Ca. luteus, Tympanis inflata, Variabilispora flava, Vexillomyces palatinus and V. verruculosus.

Imaging the neuroplastic effects of ketamine with VBM and the necessity of placebo control.

In the last years a plethora of studies have investigated morphological changes induced by behavioural or pharmacological interventions using structural T1-weighted MRI and voxel-based morphometry (VBM). Ketamine is thought to exert its antidepressant action by restoring neuroplasticity. In order to test for acute impact of a single ketamine infusion on grey matter volume we performed a placebo-controlled, double-blind investigation in healthy volunteers using VBM. 28 healthy individuals underwent two MRI sessions within a timeframe of 2 weeks, each consisting of two structural T1-weighted MRIs within a single session, one before and one 45min after infusion of S-ketamine (bolus of 0.11mg/kg, followed by an maintenance infusion of 0.12mg/kg) or placebo (0.9% NaCl infusion) using a crossover design. In the repeated-measures ANOVA with time (post-infusion/pre-infusion) and medication (placebo/ketamine) as factors, no significant effect of interaction and no effect of medication was found (FWE-corrected). Importantly, further post-hoc t-tests revealed a strong "decrease" of grey matter both in the placebo and the ketamine condition over time. This effect was evident mainly in frontal and temporal regions bilaterally with t-values ranging from 4.95 to 5.31 (FWE-corrected at p<0.05 voxel level). The vulnerabilities of VBM have been repeatedly demonstrated, with reports of influence of blood flow, tissue water and direct effects of pharmacological compounds on the MRI signal. Here again, we highlight that the relationship between intervention and VBM results is apparently subject to a number of physiological influences, which are partly unknown. Future studies focusing on the effects of ketamine on grey matter should try to integrate known influential factors such as blood flow into analysis. Furthermore, the results of this study highlight the importance of a carefully performed placebo condition in pharmacological fMRI studies.

The inbreeding strategy of a solitary primate, Microcebus murinus.

Inbreeding depression may be common in nature, reflecting either the failure of inbreeding avoidance strategies or inbreeding tolerance when avoidance is costly. The combined assessment of inbreeding risk, avoidance and depression is therefore fundamental to evaluate the inbreeding strategy of a population, that is how individuals respond to the risk of inbreeding. Here, we use the demographic and genetic monitoring of 10 generations of wild grey mouse lemurs (Microcebus murinus), small primates from Madagascar with overlapping generations, to examine their inbreeding strategy. Grey mouse lemurs have retained ancestral mammalian traits, including solitary lifestyle, polygynandry and male-biased dispersal, and may therefore offer a representative example of the inbreeding strategy of solitary mammals. The occurrence of close kin among candidate mates was frequent in young females (~37%, most often the father) and uncommon in young males (~6%) due to male-biased dispersal. However, close kin consistently represented a tiny fraction of candidate mates (< 1%) across age and sex categories. Mating biases favouring partners with intermediate relatedness were detectable in yearling females and adult males, possibly partly caused by avoidance of daughter-father matings. Finally, inbreeding depression, assessed as the effect of heterozygosity on survival, was undetectable using a capture-mark-recapture study. Overall, these results indicate that sex-biased dispersal is a primary inbreeding avoidance mechanism at the population level, and mating biases represent an additional strategy that may mitigate residual inbreeding costs at the individual level. Combined, these mechanisms explain the rarity of inbreeding and the lack of detectable inbreeding depression in this large, genetically diverse population.

Gender transition affects neural correlates of empathy: A resting state functional connectivity study with ultra high-field 7T MR imaging.

Sex-steroid hormones have repeatedly been shown to influence empathy, which is in turn reflected in resting state functional connectivity (rsFC). Cross-sex hormone treatment in transgender individuals provides the opportunity to examine changes to rsFC over gender transition. We aimed to investigate whether sex-steroid hormones influence rsFC patterns related to unique aspects of empathy, namely emotion recognition and description as well as emotional contagion. RsFC data was acquired with 7Tesla magnetic resonance imaging in 24 male-to-female (MtF) and 33 female-to-male (FtM) transgender individuals before treatment, in addition to 33 male- and 44 female controls. Of the transgender participants, 15 MtF and 20 FtM were additionally assessed after 4 weeks and 4 months of treatment. Empathy scores were acquired at the same time-points. MtF differed at baseline from all other groups and assimilated over the course of gender transition in a rsFC network around the supramarginal gyrus, a region central to interpersonal emotion processing. While changes to sex-steroid hormones did not correlate with rsFC in this network, a sex hormone independent association between empathy scores and rsFC was found. Our results underline that 1) MtF transgender persons demonstrate unique rsFC patterns in a network related to empathy and 2) changes within this network over gender transition are likely related to changes in emotion recognition, -description, and -contagion, and are sex-steroid hormone independent.

[Clinical aspects and diagnostics of cerebral vasculitis]. / Klinik und Diagnostik zerebraler Vaskulitiden.

CLINICAL/METHODICAL ISSUE: Vasculitis is a rare cause of diseases of the central nervous system (CNS). Vasculitis can be divided into primary and secondary forms, of which the vast majority can be manifested in various organ systems, including the CNS. Isolated vasculitis of the CNS is limited to the CNS and clinical neurological symptoms as with the other forms of vasculitis, are headaches, encephalopathy, focal deficits and seizures. A criterion of isolated CNS vasculitis is the clinical and laboratory diagnostic exclusion of other forms of vasculitis and the involvement of other organ systems. STANDARD RADIOLOGICAL METHODS: Multiple leaps in the caliber of intracranial arteries in cerebral angiography and multiple, small contrast medium-enhanced lesions in magnetic resonance imaging (MRI) of the brain are typical findings, which, however, can also be found in other forms of vasculitis. PERFORMANCE: The only way of proving meningitis is by a biopsy of the brain meninges and parenchyma. It is necessary to make as accurate a diagnosis as possible, especially in the context of therapeutic options of immunosuppression with steroids and cyclophosphamide. ACHIEVEMENTS: Cerebral vasculitis is a rare entity but it is an important diagnosis to consider when the appropriate clinical symptoms are present. Thorough laboratory diagnostics and subsequent brain biopsy are necessary to confirm the diagnosis in order to then be able to initiate a specific treatment.

[Trauma of the lumbar spine and the thoracolumbar junction]. / Trauma der Lendenwirbelsäule und des thorakolumbalen Übergangs.

CLINICAL/METHODICAL ISSUE: Patients who have experienced high energy trauma have a particularly high risk of suffering from fractures of the thoracic and lumbar spine. The detection of spinal injuries and the correct classification of fractures before surgery are not only absolute requirements for the implementation of appropriate surgical treatment but they are also decisive for the choice of surgical procedure. STANDARD RADIOLOGICAL METHODS: By the application of spiral computed tomography (CT) crucial additional information on the morphology of the fracture can be gained in order to estimate the fracture type and possibly the indications for specific surgical treatment options. Magnetic resonance imaging (MRI) is ideally suited to provide valuable additional information regarding injuries to the discoligamentous structures of the spine. PERFORMANCE: Magerl et al. developed a comprehensive classification especially for injuries of the thoracic and lumbar spine, which was adopted by the working group for osteosynthesis (AO). This is based on a 2­pillar model of the spinal column. The classification is based on the pathomorphological characteristics of fractures recognizable by imaging. The injury pattern is of particular importance. ACHIEVEMENTS: In spinal trauma a distinction is made between stable and unstable fractures. The treatment of spinal injuries depends on the severity of the overall injury pattern. PRACTICAL RECOMMENDATIONS: Besides adequate initial treatment at the scene, a trauma CT should be immediately carried out in order that no injuries are overlooked and to ensure a rapid decision on the treatment procedure.

[Shaken baby syndrome]. / Shaken-Baby-Syndrom.

The shaken baby syndrome (SBS) or shaking trauma describes the occurrence of subdural hematoma, retinal hemorrhage and diffuse injury to the brain by vigorous shaking of an infant that has a poor prognosis. Rapid cranial acceleration and deceleration leads to tearing of bridging veins, retinal hemorrhages and diffuse brain injuries. In addition to clinical symptoms, such as irritability, feeding difficulties, somnolence, apathy, seizures, apnea and temperature regulation disorders, vomiting also occurs due to increased intracranial pressure. Milder forms of SBS often go undiagnosed and the number of unreported cases (grey area) is probably much higher. Up to 20 % of patients die within days or weeks due to SBS and survivors often show cognitive deficits and clinical symptoms, such as physical disabilities, impaired hearing, impaired vision up to blindness, epilepsy and mental retardation as well as a combination of these conditions; therefore, prevention is very important.

[Postoperative spinal column]. / Postoperative Wirbelsäule.

STANDARD PROCEDURE: As a rule, postoperative imaging is carried out after spinal interventions to document the exact position of the implant material. INFORMATION: Imaging is absolutely necessary when new clinical symptoms occur postoperatively. In this case a rebleeding or an incorrect implant position abutting a root or the spinal cord must be proven. In addition to these immediately occurring postoperative clinical symptoms, there are a number of complications that can occur several days, weeks or even months later. These include the failed back surgery syndrome, implant loosening or breakage of the material and relapse of a disc herniation and spondylodiscitis. REVIEW: In addition to knowledge of the original clinical symptoms, it is also important to know the operation details, such as the access route and the material used. RECOMMENDATION: In almost all postoperative cases, imaging with contrast medium administration and corresponding correction of artefacts by the implant material, such as the dual energy technique, correction algorithms and the use of special magnetic resonance (MR) sequences are necessary. RECOMMENDATION: In order to correctly assess the postoperative imaging, knowledge of the surgical procedure and the previous clinical symptoms are mandatory besides special computed tomography (CT) techniques and MR sequences.

Cancer spectrum and frequency among children with Noonan, Costello, and cardio-facio-cutaneous syndromes.

BACKGROUND: Somatic mutations affecting components of the Ras-MAPK pathway are a common feature of cancer, whereas germline Ras pathway mutations cause developmental disorders including Noonan, Costello, and cardio-facio-cutaneous syndromes. These 'RASopathies' also represent cancer-prone syndromes, but the quantitative cancer risks remain unknown. METHODS: We investigated the occurrence of childhood cancer including benign and malignant tumours of the central nervous system in a group of 735 individuals with germline mutations in Ras signalling pathway genes by matching their information with the German Childhood Cancer Registry. RESULTS: We observed 12 cases of cancer in the entire RASopathy cohort vs 1.12 expected (based on German population-based incidence rates). This corresponds to a 10.5-fold increased risk of all childhood cancers combined (standardised incidence ratio (SIR)=10.5, 95% confidence interval=5.4-18.3). The specific cancers included juvenile myelomonocytic leukaemia=4; brain tumour=3; acute lymphoblastic leukaemia=2; rhabdomyosarcoma=2; and neuroblastoma=1. The childhood cancer SIR in Noonan syndrome patients was 8.1, whereas that for Costello syndrome patients was 42.4. CONCLUSIONS: These data comprise the first quantitative evidence documenting that the germline mutations in Ras signalling pathway genes are associated with increased risks of both childhood leukaemia and solid tumours.

Pupillary response to percutaneous auricular vagus nerve stimulation in alcohol withdrawal syndrome: A pilot trial.

BACKGROUND: Autonomic symptoms in alcohol withdrawal syndrome (AWS) are associated with a sympathetic-driven imbalance of the autonomic nervous system. To restore autonomic balance in AWS, novel neuromodulatory approaches could be beneficial. We conducted a pilot trial with percutaneous auricular vagus nerve stimulation (pVNS) in AWS and hypothesized that pVNS will enhance the parasympathetic tone represented by a reduction of pupillary dilation in a parasympatholytic pharmacological challenge. METHODS: Thirty patients suffering from alcohol use disorder, undergoing AWS, and stable on medication, were recruited in this open-label, single-arm pilot trial with repeated-measure design. Peripheral VNS (monophasic volt impulses of 1 msec, alternating polarity, frequency 1 Hz, amplitude 4 mV) was administered at the left cymba conchae for 72 h, followed by pupillometry under a tropicamide challenge. We assessed craving with a visual analog scale. We used pupillary mean as the dependent variable in a repeated-measures ANOVA (rmANOVA). RESULTS: A repeated-measures ANOVA resulted in a significant difference for pupillary diameter across time and condition (F(2,116) = 27.97, p < .001, ηp2 > .14). Tukey-adjusted post hoc analysis revealed a significant reduction of pupillary diameter after pVNS. Alcohol craving was significantly reduced after pVNS (p < .05, Cohen's d = 1.27). CONCLUSION: Our study suggests that pVNS activates the parasympathetic nervous system in patients with acute AWS, and that this activation is measurable by pupillometry. To this end, pVNS could be beneficial as a supportive therapy for AWS. Potential confounding effects of anti-craving treatment should be kept in mind.

Mama's boy: sex differences in juvenile survival in a highly dimorphic large mammal, the Galapagos sea lion.

In many mammals, early survival differs between the sexes, with males proving the more fragile sex ["Fragile male (FM) hypothesis"], especially in sexually dimorphic species where males are the larger sex. Male-biased allocation (MBA) by females may offset this difference. Here, we evaluate support for the FM and MBA hypotheses using a dataset on Galapagos sea lions (Zalophus wollebaeki). We statistically model sex-specific survival as it depends on body mass and environmental conditions (sea surface temperature, SST, a correlate of marine productivity) at three developmental stages, the perinatal phase (1st month), the main lactation period (1st year), and the weaning period (2nd year). Supporting the FM hypothesis, we found that, early in life (1st month), at equal birth mass, males survived less well than females. During the remainder of the first year of life, male survival was actually less sensitive to harsh environmental conditions than that of females, contradicting the FM hypothesis and supporting the MBA hypothesis. During the second year of life, only male survival suffered with high SSTs as predicted by the FM hypothesis. At each developmental stage, observed survival rates were almost equal for both sexes, suggesting that mothers buffer against the inherent fragility of male offspring through increased allocation, thereby masking the differences in survival prospects between the sexes.

Five novel locations of Neocentromeres in human: 18q22.1, Xq27.1∼27.2, Acro p13, Acro p12, and heterochromatin of unknown origin.

Since the first report in 1993, an ectopic centromere, i.e. neocentromere formation, has been reported in more than 100 small supernumerary marker chromosomes (sSMC), in 7 instances of centromere repositioning, and in about a dozen cases with more complex chromosomal rearrangements. Here we report 2 new cases with centromere repositioning and 3 neocentric sSMC consisting exclusively of heterochromatic material. Yet, no centromere formation was reported for the regions 18q22.1 and Xq27.1∼27.2 as it was observed in the 2 cases with centromere repositioning here; in both cases, cytogenetically an inversion was suggested. Two of the 3 neocentric sSMC were derived from a short arm of an acrocentric chromosome. The remainder neocentric sSMC case was previously reported and was stainable only by material derived from itself.

Escitalopram administration, relearning, and neuroplastic effects: A diffusion tensor imaging study in healthy individuals.

BACKGROUND: Neuroplastic processes are influenced by serotonergic agents, which reportedly alter white matter microstructure in humans in conjunction with learning. The goal of this double-blind, placebo-controlled imaging study was to investigate the neuroplastic properties of escitalopram and cognitive training on white matter plasticity during (re)learning as a model for antidepressant treatment and environmental factors. METHODS: Seventy-one healthy individuals (age=25.6 ± 5.0, 43 females) underwent three diffusion magnetic resonance imaging scans: at baseline, after 3 weeks of associative learning (emotional/non-emotional content), and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, participants received a daily dose of 10 mg escitalopram or placebo orally. Fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivity (RD) were calculated within the FMRIB software library and analyzed using tract-based spatial statistics. RESULTS: In a three-way repeated-measures marginal model with sandwich estimator standard errors, we found no significant effects of escitalopram and content on AD, FA, MD, and RD during both learning and relearning periods (pFDR>0.05). When testing for escitalopram or content effects separately, we also demonstrated no significant findings (pFDR>0.05) for any of the diffusion tensor imaging metrics. LIMITATIONS: The intensity of the study interventions might have been too brief to induce detectable white matter changes. DISCUSSION: Previous studies examining the effects of SSRIs on white matter tracts in humans have yielded inconclusive outcomes. Our results indicate that relearning under escitalopram does not affect the white matter microstructures in healthy individuals when administered for 3 weeks.

New species of Phaeomoniellales from a German vineyard and their potential threat to grapevine (Vitis vinifera) health.

Recently, the order Phaeomoniellales was established that includes fungi closely related to Phaeomoniella chlamydospora, a phytopathogen assumed to be the main causal agent of the two most destructive grapevine trunk diseases, Petri disease and esca. Other species of this order are reported as pathogens of other economically important crops, like olive, peach, apricot, cherry, plum, rambutan, lichee or langsat. However, they are rarely isolated and hence, little is known about their ecological traits and pathogenicity. During a 1-yr period of spore trapping in a German vineyard divided in minimally and intensively pruned grapevines, 23 fungal strains of the Phaeomoniellales were collected. Based on morphological and molecular (ITS, LSU and tub2) analyses the isolated strains were assigned to eight different species. Two species were identified as P. chlamydospora and Neophaeomoniella zymoides, respectively. The remaining six species displayed morphological and molecular differences to known species of the Phaeomoniellales and are newly described, namely Aequabiliella palatina, Minutiella simplex, Moristroma germanicum, Mo. palatinum, Neophaeomoniella constricta and N. ossiformis. A pathogenicity test conducted in the greenhouse revealed that except for P. chlamydospora, none of the species of the Phaeomoniellales isolated from spore traps is able to induce lesions in grapevine wood.

The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI. METHODS: With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions. DISCUSSION: The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Lethal cutis laxa with contractural arachnodactyly, overgrowth and soft tissue bleeding due to a novel homozygous fibulin-4 gene mutation.

Cutis laxa is characterised by redundant, inelastic skin with deep wrinkling and additional variable systemic involvement. Mutations in fibulin-4 (EFEMP2) and fibulin-5 (FBLN5) were described to be causative for autosomal recessive cutis laxa type 1 in a few families each. The female patient was born to healthy consanguineous parents. Pregnancy was remarkable for fetal overgrowth and oligohydramnios. The newborn girl showed extreme bradycardia and died perinatally. Apart from overgrowth, cutis laxa, arachnodactyly of hands and feet with contractures of the third to fifth finger, medial rotation of feet, spina bifida of the os sacrum, microcephaly and facial dysmorphism were noted. Autopsy showed collapsed lungs with hypoplastic diaphragm and signs of cervical soft tissue bleedings due to fragility of vessels. Histologic examination showed fragmentation of elastic fibres with formation of cystic cavities in the medial layer of the aorta and central lung vessels. Sequencing of the elastin, fibulin-4 and fibulin-5 genes revealed a homozygous missense mutation (p.Cys267Tyr) in the fibulin-4 gene in the patient. Our observation increases the number of cases with fibulin-4 mutations to three and extends the phenotypic spectrum of fibulin-4 mutations by microcephaly, overgrowth and arachnodactyly.

[Synchronising school entry health examinations in Lower-Saxony, Germany]. / Synchronisierung von Schuleingangsuntersuchungen in Niedersachsen.

BACKGROUND: In the German federal state of Lower-Saxony the districts are responsible for conducting school entry health examinations. There exist two different standard protocols for diagnosis and documentation, denoted as Weser-Ems (WE) and SOPHIA. In order to analyse and improve the comparability between these two protocols, a working group was established in 2006. One of the objectives was to adjust the protocols in such a way that in the future the collected data will allow for joint health reporting. METHODS: Each variable was discussed individually by the working group, and if diagnosis or documentation differed between the two protocols, specific modifications were proposed. For certain variables external expert opinions were obtained. For those variables that had to be revised quite generally, specific sub-working groups were established. As prerequisite for implementation, the recommendations of the working group had to be accepted by the user groups through majority votes. RESULTS: Of 88 (WE) or, respectively, 66 (SOPHIA) variables, 39 (WE) or, respectively, 34 variables initially fulfilled the requirements for a joint analysis. As a result of the working group, for more than 20 other variables the requirements for a joint analysis could be achieved. As soon as the sub-working groups have completed their work, also the issues of physical coordination, cognitive abilities and psychological health will be available for joint analysis. DISCUSSION: The synchronisation of school entry health examinations in Lower-Saxony is an example of how different protocols of diagnosis and documentation can be adapted to each other to enable joint data analysis without loosing their individual characteristics.

The influence of the rs6295 gene polymorphism on serotonin-1A receptor distribution investigated with PET in patients with major depression applying machine learning.

Major depressive disorder (MDD) is the most common neuropsychiatric disease and despite extensive research, its genetic substrate is still not sufficiently understood. The common polymorphism rs6295 of the serotonin-1A receptor gene (HTR1A) is affecting the transcriptional regulation of the 5-HT1A receptor and has been closely linked to MDD. Here, we used positron emission tomography (PET) exploiting advances in data mining and statistics by using machine learning in 62 healthy subjects and 19 patients with MDD, which were scanned with PET using the radioligand [carbonyl-11C]WAY-100635. All the subjects were genotyped for rs6295 and genotype was grouped in GG vs C allele carriers. Mixed model was applied in a ROI-based (region of interest) approach. ROI binding potential (BPND) was divided by dorsal raphe BPND as a specific measure to highlight rs6295 effects (BPDiv). Mixed model produced an interaction effect of ROI and genotype in the patients' group but no effects in healthy controls. Differences of BPDiv was demonstrated in seven ROIs; parahippocampus, hippocampus, fusiform gyrus, gyrus rectus, supplementary motor area, inferior frontal occipital gyrus and lingual gyrus. For classification of genotype, 'RandomForest' and Support Vector Machines were used, however, no model with sufficient predictive capability could be computed. Our results are in line with preclinical data, mouse model knockout studies as well as previous clinical analyses, demonstrating the two-pronged effect of the G allele on 5-HT1A BPND for, we believe, the first time. Future endeavors should address epigenetic effects and allosteric heteroreceptor complexes. Replication in larger samples of MDD patients is necessary to substantiate our findings.

Default mode network deactivation during emotion processing predicts early antidepressant response.

Several previous functional magnetic resonance imaging (fMRI) studies have demonstrated the predictive value of brain activity during emotion processing for antidepressant response, with a focus on clinical outcome after 6-8 weeks. However, longitudinal studies emphasize the paramount importance of early symptom improvement for the course of disease in major depressive disorder (MDD). We therefore aimed to assess whether neural activity during the emotion discrimination task (EDT) predicts early antidepressant effects, and how these predictive measures relate to more sustained response. Twenty-three MDD patients were investigated once with ultrahigh-field 7T fMRI and the EDT. Following fMRI, patients received Escitalopram in a flexible dose schema and were assessed with the Hamilton Depression Rating Scale (HAMD) before, and after 2 and 4 weeks of treatment. Deactivation of the precuneus and posterior cingulate cortex (PCC) during the EDT predicted change in HAMD scores after 2 weeks of treatment. Baseline EDT activity was not predictive of HAMD change after 4 weeks of treatment. The precuneus and PCC are integral components of the default mode network (DMN). We show that patients who exhibit stronger DMN suppression during emotion processing are more likely to show antidepressant response after 2 weeks. This is, to our knowledge, the first study to show that DMN activity predicts early antidepressant effects. However, DMN deactivation did not predict response at 4 weeks, suggesting that our finding is representative of early, likely treatment-related, yet unspecific symptom improvement. Regardless, early effects may be harnessed for optimization of treatment regimens and patient care.