Microglial function interacts with the environment to affect sex-specific depression risk.

There is a two-fold higher incidence of depression in females compared to men with recent studies suggesting a role for microglia in conferring this sex-dependent depression risk. In this study we investigated the nature of this relation. Using GWAS enrichment, gene-set enrichment analysis and Mendelian randomization, we found minimal evidence for a direct relation between genes functionally related to microglia and sex-dependent genetic risk for depression. We then used expression quantitative trait loci and single nucleus RNA-sequencing resources to generate polygenic scores (PGS) representative of individual variation in microglial function in the adult (UK Biobank; N = 54753-72682) and fetal (ALSPAC; N = 1452) periods. The adult microglial PGS moderated the association between BMI (UK Biobank; beta = 0.001, 95 %CI 0.0009 to 0.003, P = 7.74E-6) and financial insecurity (UK Biobank; beta = 0.001, 95 %CI 0.005 to 0.015, P = 2E-4) with depressive symptoms in females. The fetal microglia PGS moderated the association between maternal prenatal depressive symptoms and offspring depressive symptoms at 24 years in females (ALSPAC; beta = 0.04, 95 %CI 0.004 to 0.07, P = 0.03). We found no evidence for an interaction between the microglial PGS and depression risk factors in males. Our results illustrate a role for microglial function in the conferral of sex-dependent depression risk following exposure to a depression risk factor.

Examining the associations between microglia genetic capacity, early life exposures and white matter development at the level of the individual.

There are inter-individual differences in susceptibility to the influence of early life experiences for which the underlying neurobiological mechanisms are poorly understood. Microglia play a role in environmental surveillance and may influence individual susceptibility to environmental factors. As an index of neurodevelopment, we estimated individual slopes of mean white matter fractional anisotropy (WM-FA) across three time-points (age 4.5, 6.0, and 7.5 years) for 351 participants. Individual variation in microglia reactivity was derived from an expression-based polygenic score(ePGS) comprised of Single Nucleotide Polymorphisms (SNPs) functionally related to the expression of microglia-enriched genes.A higher ePGS denotes an increased genetic capacity for the expression of microglia-related genes, and thus may confer a greater capacity to respond to the early environment and to influence brain development. We hypothesized that this ePGS would associate with the WM-FA index of neurodevelopment and moderate the influence of early environmental factors.Our findings show sex dependency, where a significant association between WM-FA and microglia ePGS was only obtained for females.We then examined associations with perinatal factors known to decrease (optimal birth outcomes and familial conditions) or increase (systemic inflammation) the risk for later mental health problems.In females, individuals with high microglia ePGS showed a negative association between systemic inflammation and WM-FA and a positive association between more advantageous environmental conditions and WM-FA. The microglia ePGS in females thus accounted for variations in the influence of the quality of the early environment on WM-FA.Finally, WM-FA slopes mediated the association of microglia ePGS with interpersonal problems and social hostility in females. Our findings suggest the genetic capacity for microglia function as a potential factor underlying differential susceptibility to early life exposuresthrough influences on neurodevelopment.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

OBJECTIVE: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems. METHOD: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years. RESULTS: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047). CONCLUSION: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems. PLAIN LANGUAGE SUMMARY: In the S-PRESTO population-based cohort study conducted in Singapore with 351 women and their children, higher levels of maternal perceived stress within the year before pregnancy were associated with increased dendritic complexity within offsprings' nucleus accumbens, indicative of a more advanced developmental profile. Variations in right nucleus accumbens microstructure significantly modulated the association between maternal perceived stress at preconception and externalizing behaviors in early childhood. Study findings suggest that maternal stress in the preconception period accelerates in-utero nucleus accumbens development, leading to differential risk to externalizing problems in later childhood.

Screen time, brain network development and socio-emotional competence in childhood: moderation of associations by parent-child reading.

BACKGROUND: Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent-child reading in mitigating the effects of screen time. METHODS: We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent-child reading time was a moderator of the link between screen time and brain network topology. RESULTS: Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent-child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (ß = -0.640, p = 0.005). CONCLUSION: Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent-child reading in moderating the association between screen time and topological brain restructuring in early childhood.

Sensory gating, neurocognition, social cognition and real-life functioning: a 2-year follow-up of early psychosis.

BACKGROUND: Diminished sensory gating (SG) is a robust finding in psychotic disorders, but studies of early psychosis (EP) are rare. It is unknown whether SG deficit leads to poor neurocognitive, social, and/or real-world functioning. This study aimed to explore the longitudinal relationships between SG and these variables. METHODS: Seventy-nine EP patients and 88 healthy controls (HCs) were recruited at baseline. Thirty-three and 20 EP patients completed 12-month and 24-month follow-up, respectively. SG was measured using the auditory dual-click (S1 & S2) paradigm and quantified as P50 ratio (S2/S1) and difference (S1-S2). Cognition, real-life functioning, and symptoms were assessed using the MATRICS Consensus Cognitive Battery, Global Functioning: Social (GFS) and Role (GFR), Multnomah Community Ability Scale (MCAS), Awareness of Social Inference Test (TASIT), and the Positive and Negative Syndrome Scale (PANSS). Analysis of variance (ANOVA), chi-square, mixed model, correlation and regression analyses were used for group comparisons and relationships among variables controlling for potential confounding variables. RESULTS: In EP patients, P50 ratio (p < 0.05) and difference (p < 0.001) at 24-month showed significant differences compared with that at baseline. At baseline, P50 indices (ratio, S1-S2 difference, S1) were independently associated with GFR in HCs (all p < 0.05); in EP patients, S2 amplitude was independently associated with GFS (p = 0.037). At 12-month and 24-month, P50 indices (ratio, S1, S2) was independently associated with MCAS (all p < 0.05). S1-S2 difference was a trending predictor of future function (GFS or MCAS). CONCLUSIONS: SG showed progressive reduction in EP patients. P50 indices were related to real-life functioning.

Oncology-related emergencies discharged from the emergency department.

Introduction: Cancer patients attending emergency departments (EDs) often present with acute symptoms and are frequently admitted. This study aimed to characterise the profile of oncology patients who were discharged from the ED. Methods: This was a retrospective audit of patients with cancer-related diagnoses who presented to the ED at the Singapore General Hospital (SGH) over a 6-month period from 1 October 2018 to 31 March 2019 and were directly discharged from the ED. Data was extracted from the hospital's electronic medical record system. Results: Of the 492 participants included in the study, the majority were triaged as Priority 2 (61.4%), while 30.7% were triaged as Priority 3, 6.9% as Priority 1 and 1.0% as Priority 4. There was no statistical difference between the National Early Warning scores across the different triage categories in these patients. The most common complaint was (44.3%), followed by genitourinary symptoms (19.5%) and those related to devices, catheters or stomas (17.3%). More investigations of all types were done for patients being managed in Priority 1 (57.6%) than in the other triage categories (40.1% for Priority 2, 23.2% for Priority 3 and 12.0% for Priority 4). Treatment procedures carried out were mainly symptomatic (analgesics, antiemetics, proton pump inhibitors) for 79.8% of the patients. There were no significant differences in the proportion of patients requiring various treatment modalities among the triage categories. Conclusion: Selected oncological patients may potentially be managed in an ambulatory setting.

Functional connectivity analysis of childhood depressive symptoms.

BACKGROUND: Childhood depression is a highly distinct and prevalent condition with an unknown neurobiological basis. We wish to explore the resting state fMRI data in children for potential associations between neural connectivity and childhood depressive symptoms. METHODS: A longitudinal birth cohort study with neuroimaging data obtained at 4.5, 6.0 and 7.5 years of age and the Children Depression Inventory 2 (CDI) administered between 8.5 and 10.5 years was used. The CDI score was used as the dependent variable and tested for correlation, both simple Pearson and network based statistic, with the functional connectivity values obtained from the resting state fMRI. Cross-validated permutation testing with a general linear model was used to validate that the identified functional connections were indeed implicated in childhood depression. RESULTS: Ten functional connections and four brain regions (Somatomotor Area B, Temporoparietal Junction, Orbitofrontal Cortex and Insula) were identified as significantly associated with childhood depressive symptoms for girls at 6.0 and 7.5 years. No significant functional connections were found in girls at 4.5 years or for boys at any timepoint. Network based statistic and permutation testing confirmed these findings. CONCLUSIONS: This study revealed significant sex-dependent associations of neural connectivity and childhood depressive symptoms. The regions identified are implicated in speech/language, social cognition and information integration and suggest unique pathways to childhood depressive symptoms.

Exploring the influence of functional architecture on cortical thickness networks in early psychosis - A longitudinal study.

Cortical thickness reductions differ between individuals with psychotic disorders and comparison subjects even in early stages of illness. Whether these reductions covary as expected by functional network membership or simply by spatial proximity has not been fully elucidated. Through orthonormal projective non-negative matrix factorization, cortical thickness measurements in functionally-annotated regions from MRI scans of early-stage psychosis and matched healthy controls were reduced in dimensionality into features capturing positive covariance. Rather than matching the functional networks, the covarying regions in each feature displayed a more localized spatial organization. With Bayesian belief networks, the covarying regions per feature were arranged into a network topology to visualize the dependency structure and identify key driving regions. The features demonstrated diagnosis-specific differences in cortical thickness distributions per feature, identifying reduction-vulnerable spatial regions. Differences in key cortical thickness features between psychosis and control groups were delineated, as well as those between affective and non-affective psychosis. Clustering of the participants, stratified by diagnosis and clinical variables, characterized the clinical traits that define the cortical thickness patterns. Longitudinal follow-up revealed that in select clusters with low baseline cortical thickness, clinical traits improved over time. Our study represents a novel effort to characterize brain structure in relation to functional networks in healthy and clinical populations and to map patterns of cortical thickness alterations among ESP patients onto clinical variables for a better understanding of brain pathophysiology.

Subfield-specific longitudinal changes of hippocampal volumes in patients with early-stage bipolar disorder.

BACKGROUND: The hippocampus is a heterogeneous structure composed of biologically and functionally distinct subfields. Hippocampal aberrations are proposed to play a fundamental role in the etiology of psychotic symptoms. Bipolar disorder (BPD) has substantial overlap in symptomatology and genetic liability with schizophrenia (SZ), and reduced hippocampal volumes, particularly at the chronic illness stages, are documented in both disorders. Studies of hippocampal subfields in the early stage of BPD are limited and cross-sectional findings to date report no reduction in hippocampal volumes. To our knowledge, there have been no longitudinal studies of BPD evaluating hippocampal volumes in the early phase of illness. We investigated the longitudinal changes in hippocampal regions and subfields in BPD mainly and in early stage of psychosis (ESP) patients more broadly and compared them to those in controls (HC). METHODS: Baseline clinical and structural MRI data were acquired from 88 BPD, from a total of 143 ESP patients, and 74 HCs. Of those, 66 participants (23 HC, 43 patients) completed a 12-month follow-up visit. The hippocampus regions and subfields were segmented using Freesurfer automated pipeline. RESULTS: We found general baseline deficits in hippocampal volumes among BPD and ESP cohorts. Both cohorts displayed significant increases in the anterior hippocampal region and dentate gyrus compared with controls. Additionally, antipsychotic medications were positively correlated with the posterior region at baseline. CONCLUSION: These findings highlight brain plasticity in BPD and in ESP patients providing evidence that deviations in hippocampal volumes are adaptive responses to atypical signaling rather than progressive degeneration.

Impact of Substance Use Disorder on Between-Network Brain Connectivity in Early Psychosis.

The Triple Network Model of psychopathology identifies the salience network (SN), central executive network (CEN), and default mode network (DMN) as key networks underlying the pathophysiology of psychiatric disorders. In particular, abnormal SN-initiated network switching impacts the engagement and disengagement of the CEN and DMN, and is proposed to lead to the generation of psychosis symptoms. Between-network connectivity has been shown to be abnormal in both substance use disorders (SUD) and psychosis. However, none have studied how SUD affects connectivity between sub-networks of the DMN, SN, and CEN in early stage psychosis (ESP) patients. In this study, we collected data from 113 ESP patients and 50 healthy controls to investigate the effect of SUD on between-network connectivity. In addition, we performed sub-group analysis by exploring whether past SUD vs current SUD co-morbidity, or diagnosis (affective vs non-affective psychosis) had a modulatory effect. Connectivity between four network-pairs, consisting of sub-networks of the SN, CEN, and DMN, was significantly different between ESP patients and controls. Two patterns of connectivity were observed when patients were divided into sub-groups with current vs past SUD. In particular, connectivity between right CEN and the cingulo-opercular salience sub-network (rCEN-CON) showed a gradient effect where the severity of abnormalities increased from no history of SUD to past+ to current+. We also observed diagnosis-specific effects, suggesting non-affective psychosis patients were particularly vulnerable to effects of substance use on rCEN-CON connectivity. Our findings reveal insights into how comorbid SUD affects between-network connectivity and symptom severity in ESP.

Structure-function coupling within the reward network in preschool children predicts executive functioning in later childhood.

Early differences in reward behavior have been linked to executive functioning development. The nucleus accumbens (NAc) and orbitofrontal cortex (OFC) are activated by reward-related tasks and identified as key nodes of the brain circuit that underlie reward processing. We aimed to investigate the relation between NAc-OFC structural and functional connectivity in preschool children, as well as associations with future reward sensitivity and executive function. We showed that NAc-OFC structural and functional connectivity were not significantly associated in preschool children, but both independently predicted sensitivity to reward in males in a left-lateralized manner. Moreover, significant NAc-OFC structure-function coupling was only found in individuals who performed poorly on executive function tasks in later childhood, but not in the middle- and high-performing groups. As structure-function coupling is proposed to measure functional specialization, this finding suggests premature functional specialization within the reward network, which may impede dynamic communication with other regions, affects executive function development. Our study also highlights the utility of multimodal imaging data integration when studying the effects of reward network functional flexibility in the preschool age, a critical period in brain and executive function development.

Dynamic and progressive changes in thalamic functional connectivity over the first five years of psychosis.

The early stage of psychosis (ESP) is a critical period where effective intervention has the most favorable impact on outcomes. Thalamic connectivity abnormalities have been consistently found in psychosis, and are associated with clinical symptoms and cognitive deficits. However, most studies consider ESP patients as a homogeneous population and fail to take the duration of illness into account. In this study, we aimed to capture the progression of thalamic connectivity changes over the first five years of psychosis. Resting-state functional MRI scans were collected from 156 ESP patients (44 with longitudinal data) and 82 healthy controls (24 with longitudinal data). We first performed a case-control analysis comparing thalamic connectivity with 13 networks in the cortex and cerebellum. Next, we modelled the shape (flat, linear, curvilinear) of thalamic connectivity trajectories by comparing flexible non-linear versus linear models. We then tested the significance of the duration of illness and diagnosis in trajectories that changed over time. Connectivity changed over the ESP period between the thalamus and default mode network (DMN) and fronto-parietal network (FPN) nodes in both the cortex and cerebellum. Three models followed a curvilinear trajectory (early increase followed by a subsequent decrease), while thalamo-cerebellar FPN connectivity followed a linear trajectory of steady reductions over time, indicating different rates of change. Finally, diagnosis significantly predicted thalamic connectivity. Thalamo-cortical and thalamo-cerebellar connectivity change in a dynamic fashion during the ESP period. A better understanding of these changes may provide insights into the compensatory and progressive changes in functional connectivity in the early stages of illness.

Gene expression analysis of combined RNA-seq experiments using a receiver operating characteristic calibrated procedure.

Because of rapid advancements in sequencing technology, the experimental platforms of RNA-seq are updated frequently. It is quite common to combine data sets from several experimental platforms for analysis in order to increase the sample size and achieve more powerful tests for detecting the presence of differential gene expression. The data sets combined from different experimental platforms will have a complex data distribution, which causes a major problem in statistical modeling as well as in multiple testing. Although plenty of research have studied this problem by modeling the batch effects, there are no general and robust data-driven procedures for RNA-seq analysis. In this paper we propose a new robust procedure which combines the use of popular methods (packages) with a data-driven simulation (DDS). We construct the average receiver operating characteristic curve through the DDS to provide the calibrated levels of significance for multiple testing. Instead of further modifying the adjusted p-values, we calibrated the levels of significance for each specific method and mean effect model. The procedure was demonstrated with several popular RNA-seq analysis methods (edgeR, DEseq2, limma+voom). The proposed procedure relaxes the stringent assumptions of data distributions for RNA-seq analysis methods and is illustrated using colorectal cancer studies from The Cancer Genome Atlas database.

Heterogeneity of Outcomes and Network Connectivity in Early-Stage Psychosis: A Longitudinal Study.

Imaging studies in psychotic disorders typically examine cross-sectional relationships between magnetic resonance imaging (MRI) signals and diagnosis or symptoms. We sought to examine changes in network connectivity identified using resting-state functional MRI (fMRI) corresponding to divergent functional recovery trajectories and relapse in early-stage psychosis (ESP). Prior studies have linked schizophrenia to hyperconnectivity in the default mode network (DMN). Given the correlations between the DMN and behavioral impairments in psychosis, we hypothesized that dynamic changes in DMN connectivity reflect the heterogeneity of outcomes in ESP. Longitudinal data were collected from 66 ESP patients and 20 healthy controls. Longitudinal cluster analysis identified subgroups of patients with similar trajectories in terms of symptom severity and functional outcomes. DMN connectivity was measured in a subset of patients (n = 36) longitudinally over 2 scans separated by a mean of 12 months. We then compared connectivity between patients and controls, and among the different outcome trajectory subgroups. Among ESP participants, 4 subgroups were empirically identified corresponding to: "Poor," "Middle," "Catch-up," and "Good" trajectory outcomes in the complete dataset (n = 36), and an independent replication (n = 30). DMN connectivity changes differed significantly between functional subgroups (F3,32 = 6.06, P-FDR corrected = .01); DMN connectivity increased over time in the "Poor" outcome cluster (ß = +0.145) but decreased over time in the "Catch-up" cluster (ß = -0.212). DMN connectivity is dynamic and correlates with a change in functional status over time in ESP. This approach identifies a brain-based marker that reflects important neurobiological processes required to sustain functional recovery.

Post-inflammatory behavioural despair in male mice is associated with reduced cortical glutamate-glutamine ratios, and circulating lipid and energy metabolites.

Post-inflammatory behaviours in rodents are widely used to model human depression and to test the efficacy of novel anti-depressants. Mice injected with lipopolysaccharide (LPS) display a depressive-like phenotype twenty-four hours after endotoxin administration. Despite the widespread use of this model, the mechanisms that underlie the persistent behavioural changes after the transient peripheral inflammatory response remain elusive. The study of the metabolome, the collection of all the small molecule metabolites in a sample, combined with multivariate statistical techniques provides a way of studying biochemical pathways influenced by an LPS challenge. Adult male CD-1 mice received an intraperitoneal injection of either LPS (0.83 mg/kg) or saline, and were assessed for depressive-like behaviour 24 h later. In a separate mouse cohort, pro-inflammatory cytokine gene expression and 1H nuclear magnetic resonance (NMR) metabolomics measurements were made in brain tissue and blood. Statistical analyses included Independent Sample t-tests for gene expression data, and supervised multi-variate analysis using orthogonal partial least squares discriminant analysis for metabolomics. Both plasma and brain metabolites in male mice were altered following a single peripheral LPS challenge that led to depressive-like behaviour in the forced swim test. The plasma metabolites altered by LPS are involved in energy metabolism, including lipoproteins, glucose, creatine, and isoleucine. In the brain, glutamate, serine, and N-acetylaspartate (NAA) were reduced after LPS, whereas glutamine was increased. Serine-modulated glutamatergic signalling and changes in bioenergetics may mediate the behavioural phenotype induced by LPS. In light of other data supporting a central imbalance of glutamate-glutamine cycling in depression, our results suggest that aberrant central glutaminergic signalling may underpin the depressive-like behaviours that result from both inflammation and non-immune pathophysiology. Normalising glutaminergic signalling, rather than seeking to increase serotonergic signalling, might prove to be a more coherent approach to the development of new treatments for mood disorder.

Reorganising the emergency department to manage the COVID-19 outbreak.

BACKGROUND: The COVID-19 disease outbreak that first surfaced in Wuhan, China, in December 2019, has taken the world by storm and ravaged almost every country in the world. Emergency departments (ED) in hospitals are on the frontlines, serving an essential function in identifying these patients, isolating them early whilst providing urgent medical care. This outbreak has reinforced the role of Emergency Medicine in public health. This paper documents the challenges faced and measures taken by a tertiary hospital's ED in Singapore, in response to the outbreak. MAIN BODY: The ED detected the first case of COVID-19 in Singapore on 22 January 2020 in a Chinese tourist and also the first case of locally transmitted COVID-19 on 3 February 2020. The patient journeys through the patient reception area in the ED and undergoes fever screening before being shunted to isolation areas within the ED. Management and disposition of suspect COVID-19 patients are guided by a close-knit collaboration between ED and department of infectious diseases. With increasing number of patients, back-up plans for expansion of space and staff augmentation have been enacted. Staff safety is also of utmost importance, with provision and guidelines for personal protective equipment and team segregation to ensure no cross-contamination across staff. These have been made possible with an early setup of an operational command and control structure within the ED, managing manpower, logistics, operations, communication and information management and liaison with other clinical departments. CONCLUSION: With the large numbers of undifferentiated patients managed by the ED to date, more than 820 patients with COVID-19 have been identified in the hospital. Not a single member of the staff of the SGH Emergency Department has come down with the illness. The various measures undertaken by the department have helped to ensure good staff morale and strict adherence to safety procedures. We share the lessons learnt so that others who manage EDs around the world can benefit from our experience.

A single administration of the antibiotic, minocycline, reduces fear processing and improves implicit learning in healthy volunteers: analysis of the serum metabolome.

Minocycline has shown therapeutic promise in pre-clinical animal models and early phase clinical trials for a variety of psychiatric disorders. Previous studies on minocycline have shown its ability to suppress microglia activity and reduce inflammatory cytokine levels, and its amelioration of depressive-like behaviour in animals and humans. However, the underlying mechanisms that lead to minocycline's psychotropic effects are not clear. In this study, we investigated the psychological and biochemical effects of an acute dose of minocycline or placebo in 40 healthy adult volunteers. Psychological changes in emotional processing, implicit learning, and working memory were assessed. Plasma inflammatory markers, measured with enzyme-linked immunosorbent assays, and serum metabolites, measured with proton nuclear magnetic resonance combined with multi-variate analysis techniques, were also studied. Results showed that minocycline administration decreased fear misclassification and increased contextual learning, which suggested that reducing negative biases and improving cognition, respectively, may underlie the antidepressant actions of this agent. An examination of serum metabolites revealed higher levels of lipoproteins, particularly cholesterol, in the minocycline group. Minocycline also decreased circulating concentrations of the inflammatory marker C-Reactive Peptide, which is consistent with previous research. These effects highlight two important psychological mechanisms that may be relevant to the efficacy of minocycline reported in clinical trials, and also suggest a possible largely unexplored lipid-related biochemical pathway for the action of this drug.

Clinical features of 42 cases of COVID-19 / 上海预防医学

Objective To investigate the clinical features, laboratory findings, chest CT findings and treatment of patients with COVID-19, and to analyze their relationship with prognosis. Methods From January to February 2020, the clinical data on the 42 patients with COVID-19 admitted to the Wenzhou Sixth People′s Hospital were analyzed retrospectively. Results The clinical symptoms of the 42 cases included fever (35 cases), cough (26 cases), fatigue (14 cases), aspiration (9 cases), sore throat (4 cases), muscle ache (5 cases), headache (2 cases), nausea (4 cases), diarrhea (6 cases) and abdominal pain (1 case).The absolute number of blood lymphocyte decreased to different degrees in 22 cases.Fourteen cases had lactate dehydrogenase obviously, with no obvious change in procalcitonin.The imaging manifestations were cloud-like and ground-glass-like high density shadows scattered outside the lungs, small flaky consolidation and bronchus inflating sign were seen locally.A few images showed diffuse high density, most of the lesions showed consolidation or striate change, and local fibrosis was formed in the lower lobes of both lungs. Conclusion Fever and cough are the first symptoms of COVID-19, and a few cases are associated with shortness of breath and diarrhea, accompanied by different degrees of systemic symptoms, but most of the patients improve their conditions after active antivirus, anti-infection, systematic symptoms improvement and supportive treatment.The disease is highly infectious and its condition changes rapidly.Therefore, early detection, early diagnosis and comprehensive treatment of the whole body as soon as possible are the keys to treatment.

Varicella meningitis with concomitant genital shingles in an adolescent.

This case describes an uncommon presentation of herpes zoster in an adolescent with viral meningitis and concomitant genital shingles. A 15-year-old immunocompetent girl with background of well-controlled Graves' disease presented with 3 days of fever, frontal headache, terminal neck stiffness and photophobia. This was preceded by 4 days of pain and itch over vaginal and anal region. She had one dose of varicella vaccination at 18 months old and developed mild primary varicella infection around 5 years of age. Varicella zoster virus DNA was detected both in cerebrospinal fluid and in vesicles over her right labial majora. While there is no international consensus on the recommended duration of treatment for zoster with neurological complications, she was treated with intravenous acyclovir for 10 days with good clinical response. Her fever, headache and neck stiffness resolved after 2 days and genital lesions resolved after 9 days of antiviral therapy.

The Influence of Ethnicity on Exclusively Breast-Fed Infants' Anthropometry in a Multiethnic Asian Population.

INTRODUCTION: We studied the effects of ethnicity on early infant growth patterns in exclusively breast-fed (EBF) infants from a Singaporean multiethnic population. This was a prospective cohort study conducted in National University Hospital, Singapore. MATERIALS AND METHODS: Healthy, EBF infants born at-term completing 37 weeks and above, and whose birthweight was appropriate for gestational age (>10th centile, <90th centile) were recruited. Infants were required to be EBF at least until the minimum age of weaning. All infants who were preterm and premature, formula-fed, required Intensive/High Dependency care, or born with major congenital anomalies were excluded. A multivariable linear regression analysis was conducted at 5 predetermined time-points (birth; 4-8 weeks; 3-4, 5-8, 12 months) to study the effects of antenatal/parental factors on infant growth. RESULTS: A total of 213 infants were recruited. Maternal age, height and body mass index positively influenced birthweights while maternal hypertension and paternal smoking negatively influenced birthweights. Mean duration of breastfeeding was 8.9 months. Chinese ethnicity did not influence birth anthropometry, but was the single consistent factor that significantly increased weight and length Z-scores from 4-8 weeks until 8 months of life. Chinese ethnicity did not influence head growth throughout the first year of life. CONCLUSION: EBF Chinese infants have increased weights and lengths compared to non-Chinese infants until 8 months' age, despite similar birth anthropometry. This period of discrepant growth coincides with the average duration of breastfeeding. We hypothesise that ethnic variations in breast milk macronutrient composition influence early somatic growth in infants.