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Bovine mastitis harms milk quality and cattle health. Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) are well-known milk-derived bioactive peptides with anti-inflammatory activity. However, the impact of VPP and IPP on mastitis remain unknown. This study aimed to investigate the anti-inflammatory effects and the underlying mechanisms of VPP and IPP in lipopolysaccharide (LPS)-induced inflammation. When cells were treated with LPS (1 µg/mL) for 24 h, the protein levels of pro-inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin(IL)-1β and IL-6)) and chemokine (monocyte chemotactic protein-1 (MCP-1)) were markedly increased, and the protein level of anti-inflammatory cytokine (IL-10) was reduced. Both VPP and IPP with concentrations of 50 and 100 µM reversed these phenomena and further inhibited the protein expression of β-casein induced by LPS. In a mouse mastitis model, different concentrations of VPP and IPP (300, 600 µM/kg) pretreatment alleviated histopathological lesions in the mammary gland and suppressed the mRNA expression of TNFα, IL1β, and IL6 induced by LPS. VPP and IPP also maintained the integrity of the blood–milk barrier in mice. RNA-seq analyses indicated that enriched phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways likely contribute to the changes observed (P < 0.05 and |log2 fold change (FC)| ≥ 1). Notably, fibronectin was identified as an important hub by protein–protein interaction (PPI) analysis and molecular docking combined with molecular dynamics simulation. In summary, VPP and IPP exerted a protective effect on LPS-induced inflammation by regulating PI3K/AKT signaling pathway via fibronectin.
Contrafreeloading (CFL) refers to animals’ tendency to prefer obtaining food through effort rather than accessing food that is freely available. Researchers have proposed various hypotheses to explain this intriguing phenomenon, but few studies have provided a comprehensive analysis of the factors influencing this behaviour. In this study, we observed the choice of alternative food containers in budgerigars (Melopsittacus undulatus) to investigate their CFL tendencies and the effects of pre-training, food deprivation, and effort required on the CFL tasks. The results showed that budgerigars did not exhibit significant difference in their first choices or the time interacting with less challenging versus more challenging food containers. Moreover, when evaluating each budgerigar’s CFL level, only half of them were identified as strong contrafreeloaders. Thus, we suggest that budgerigars exhibit an intermediate CFL level that lies somewhere between a strong tendency and the absence of such behaviour. Furthermore, we also found that food-deprived budgerigars tended to select less challenging food containers, and pre-trained budgerigars were more likely to choose highly challenging food containers than moderately challenging food containers, which means that the requirement of only a reasonable effort (access to food from moderately challenging food containers in this study) and the experience of pre-training act to enhance their CFL levels, whereas the requirement of greater effort and the experience of food deprivation act to decrease their CFL levels. Studying animal CFL can help understand why animals choose to expend effort to obtain food rather than accessing it for free, and it also has implications for setting feeding environments to enhance the animal welfare of captive and domesticated animals.
This study aimed to investigate the intake of dairy products during pregnancy in women with gestational diabetes mellitus (GDM) and its impacts on neonatal birth weight and pregnancy outcomes. A total of 386 women with GDM during the second trimester pregnancy participated in this prospective cohort study. We evaluated dairy products intake through the FFQ. Pregnancy outcomes were obtained from the delivery data. Participants were divided into insufficient and sufficient intake of milk and dairy products groups (< 300 g/d and ≥ 300 g/d, respectively). The average intake of dairy products during the second trimester pregnancy in women with GDM was 317·8 ± 179·5 g/d, and the total energy intake was 1635·4 ± 708·7 kcal/d. However, 76·68 % of them did not meet the recommended total energy intake of women with GDM. After adjusting for confounding factors, women with GDM who consumed ≥ 300 g/d of dairy products had an average reduction in birth weight of 93·1 g compared with women who consumed < 300 g/d of dairy products (95 % CI −171·343, −14·927). Women with GDM in sufficient intake group was also associated with lower risk of macrosomia (95 % CI 0·043, 0·695) and caesarean section (95 % CI 0·387, 0·933) and not related to low birth weight infant (95 % CI 0·617, 14·502) and preterm birth (95 % CI 0·186, 1·510) when compared with participants in insufficient intake group. Under the premise of insufficient total energy intake, the intake of dairy products during the second trimester pregnancy in women with GDM might be related to the decrease of neonatal birth weight.
Post-traumatic stress disorder (PTSD) is a mental health condition caused by the dysregulation or overgeneralization of memories related to traumatic events. Investigating the interplay between explicit narrative and implicit emotional memory contributes to a better understanding of the mechanisms underlying PTSD.
Methods
This case–control study focused on two groups: unmedicated patients with PTSD and a trauma-exposed control (TEC) group who did not develop PTSD. Experiments included real-time measurements of blood oxygenation changes using functional near-infrared spectroscopy during trauma narration and processing of emotional and linguistic data through natural language processing (NLP).
Results
Real-time fNIRS monitoring showed that PTSD patients (mean [SD] Oxy-Hb activation, 0.153 [0.084], 95% CI 0.124 to 0.182) had significantly higher brain activity in the left anterior medial prefrontal cortex (L-amPFC) within 10 s after expressing negative emotional words compared with the control group (0.047 [0.026], 95% CI 0.038 to 0.056; p < 0.001). In the control group, there was a significant time-series correlation between the use of negative emotional memory words and activation of the L-amPFC (latency 3.82 s, slope = 0.0067, peak value = 0.184, difference = 0.273; Spearman’s r = 0.727, p < 0.001). In contrast, the left anterior cingulate prefrontal cortex of PTSD patients remained in a state of high activation (peak value = 0.153, difference = 0.084) with no apparent latency period.
Conclusions
PTSD patients display overactivity in pathways associated with rapid emotional responses and diminished regulation in cognitive processing areas. Interventions targeting these pathways may alleviate symptoms of PTSD.
In this paper, we study the rapid transition in Richtmyer–Meshkov instability (RMI) with reshock through three-dimensional double-layer swirling vortex rings. The rapid transition in RMI with reshock has an essential influence on the evolution of supernovas and the ignition of inertial confinement fusion, which has been confirmed in numerical simulations and experiments in shock-tube and high-energy-density facilities over the past few years. Vortex evolution has been confirmed to dominate the late-time nonlinear development of the perturbed interface. However, few studies have investigated the three-dimensional characteristics and nonlinear interactions among vortex structures during the transition to turbulent flows. The coexistence of co-rotating and counter-rotating vortices is hypothesized to induce successive large-scale strain fields, which are the main driving sources for rapid development. The three-dimensional effect is reflected in the presence of local swirling motion in the azimuthal direction, and it decreases the translation velocity of a vortex ring. Large-, middle- and small-scale strain fields are employed to describe the development process of RMI with reshock, e.g. vorticity deposited by the reshock, formation of the coexistence of the co-rotating and counter-rotating vortices, iterative cascade under the amplification of the strain fields and viscous dissipation to internal energy. This provides theoretical suggestions for designing practical applications, such as the estimation of the hydrodynamic instability and mixing during the late-time acceleration phase of the inertial confinement fusion.
Caring for children with solid tumors (STs) can impact caregiver’s physical and mental health. Caregiver mastery, which influences psychological well-being, is vital in improving outcomes for both caregivers and children. The study aimed to investigate the relationship between caregiver mastery, anxiety, depression, fear of disease progression (FoP), caregiver burden, and the quality of life (QOL) of children with ST.
Methods
This cross-sectional study was conducted from June 2022 to April 2023 at a Grade A tertiary hospital in Shandong. Family caregivers of children with ST completed several validated measures, including the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module, the Fear of Progression Questionnaire-parent version (FoP-Q-SF/PR), the Zarit Burden Interview Scale (ZBI), the hospital anxiety and depression scale (HADS), and the Caregiver Mastery Scale. Multiple linear regression analyses assessed the relationships between FoP, caregiver burden, anxiety, depression, caregiver mastery, and children’s QOL. Results were expressed as β and 95% confidence intervals (CIs).
Results
A total of 454 caregivers participated. Caregiver mastery was positively correlated with children’s QOL (β = 0.80, 95% CI: 0.20 to 1.39). Depression (β = −0.64, 95% CI: −0.83 to −0.45), anxiety (β = −0.67, 95% CI: −0.85 to −0.49), caregiver burden (β = −1.20, 95% CI: −1.60 to −0.80), and FoP (β = −0.04, 95% CI: −0.05 to −0.03) were negatively related to children’s QOL. Caregiver mastery moderated the associations between depression, caregiver burden, FoP, and children’s QOL, while also improving the effect of mild anxiety on QOL.
Significance of results
The study underscores the importance of fostering caregiver mastery to mitigate the negative impact of caregiver distress on children’s QOL and improve outcomes for both caregivers and children with solid tumors.
Conclusion
Caregiver mastery moderates the effects of anxiety, depression, FoP, and caregiver burdenon children’s QOL. Supporting caregiver mastery can alleviate caregiver burden and enhance both caregiver and child well-being.
This study aims to investigate the effects of the vine of Lonicera japonica Thunb (VLT) and marine-derived Bacillus amyloliquefaciens-9 (BA-9) supplementation on the growth performance, antioxidant capacity, and gut microbiota of goat kids. A total of 32 4-week-old kids were randomly assigned into four groups: a control group (CON), a group supplemented with 0.3% BA-9 (BA-9), a group supplemented with 2% VLT (VLT), and a group supplemented with both 0.3% BA-9 and 2% VLT (MIX). The results indicated that VLT supplementation significantly increased both average daily (P < 0.001) and total weight gain (TWG) (P < 0.001), while BA-9 alone had no significant effect (P > 0.05) on the average daily and TWG. Biomarker analysis of oxidative stress revealed that supplementation of VLT or BA-9 alone enhanced antioxidant capacity. The MIX group showing a higher total antioxidant capacity (T-AOC) compared with the CON, VLT, and BA-9 groups (P < 0.05). Plasma albumin (ALB) levels were significantly increased in the both VLT and BA-9 groups. Microbiota analysis revealed significant differences in α-diversity and β-diversity between the MIX and CON groups, with specific genera such as Prevotellaceae_UCG.004 and Rikenellaceae_RC9_gut_group negatively correlated with average daily gain (ADG), while Alistipes was positively correlated with T-AOC. These findings suggest that the combined supplementation of VLT and BA-9 can significantly enhance growth performance and antioxidant capacity in goat kids by modulating the composition of gut microbiota and reducing oxidative stress.
This paper proposes an online robust self-learning terminal sliding mode control (RS-TSMC) with stability guarantee for balancing control of reaction wheel bicycle robots (RWBR) under model uncertainties and disturbances, which improves the balancing control performance of RWBR by optimising the constrained output of TSMC. The TSMC is designed for a second-order mathematical model of RWBR. Then robust adaptive dynamic programming based on an actor-critic algorithm is used to optimise the TSMC only by data sampled online. The system closed-loop stability and convergence of the neural network weights are guaranteed based on the Lyapunov analysis. The effectiveness of the proposed algorithm is demonstrated through simulations and experiments.
This study investigates the flow structures and combustion regimes in an axisymmetric cavity-based scramjet combustor with a total temperature of 1800 K and a high Reynolds number of approximately 1 × 107. The hydroxyl planar laser-induced fluorescence technique, along with the broadband flame emission and CH* chemiluminescence, is employed to visualize the instantaneous flame structure in the optically accessible cavity. The jet-wake flame stabilization mode is observed, with intense heat release occurring in the jet wake upstream of the cavity. A hybrid Reynolds-averaged Navier–Stokes/large-eddy simulation approach is performed for the 0.18-equivalent-ratio case with a pressure-corrected flamelet/progress variable model. The combustion regime is identified mainly in the corrugated or wrinkled flamelet regime (approximately 102 < Da < 104, 103 < Ret < 105 where $Da$ is the Damköhler number and $Re_t$ is the turbulent Reynolds number). The combustion process is jointly dominated by supersonic combustion (which accounts for approximately 58 %) and subsonic combustion, although subsonic combustion has a higher heat release rate (peak value exceeding 1 × 109 J (m3s)−1). A partially premixed flame is observed, where the diffusion flame packages a considerable quantity of twisted premixed flame. The shockwave plays a critical role in generating vorticity by strengthening the volumetric expansion and baroclinic torque term, and it can facilitate the chemical reaction rates through the pressure and temperature surges, thereby enhancing the combustion. Combustion also shows a remarkable effect on the overall flow structures, and it drives alterations in the vorticity of the flow field. In turn, the turbulent flow facilitates the combustion and improves the flame stabilization by enhancing the reactant mixing and increasing the flame surface area.
The maser instability associated with the loss-cone distribution has been widely invoked to explain the radio bursts observed in the astrophysical plasma environment, such as aurora and corona. In the laboratory plasma of a tokamak, events reminiscent of these radio bursts have also been frequently observed as an electron cyclotron emission (ECE) burst in the microwave range ($\mathrm{\sim }2{f_{\textrm{ce}}}$ near the last closed flux surface) during transient magnetohydrodynamic events. These bursts have a short duration of ~10 μs and display a radiation spectrum corresponding to a radiation temperature ${T_{e,\textrm{rad}}}$ of over $30\ \textrm{keV}$ while the edge thermal electron temperature ${T_e}$ is only in the range of $1\ \textrm{keV}$. Suprathermal electrons can be generated through magnetic reconnection, and a loss-cone distribution can be generated through open stochastic field lines in the magnetic mirror of the near-edge region of a tokamak plasma. Radiation modelling shows that a sharp distribution gradient $\partial f/\partial {v_ \bot } > 0$ at the loss-cone boundary can cause a negative absorption of ECE radiation through the maser instability. The negative absorption then amplifies the radiation so that the microwave intensity is significantly stronger than the thermal value. The significant ${T_{e,\textrm{rad}}}$ from the simulations suggests the potential role of the loss-cone maser instability in generating the ECE burst in a tokamak.
The formation mechanism for the stopping vortex ring (SVR) and its effects on the development of starting jets have been systematically investigated. The radial inward flow near the nozzle exit, arising from the pressure difference caused by the deceleration of starting jets, is considered to be the main contributing factor to the formation of the SVR. The formation process can generally be divided into (i) the rapid accumulation stage ($t_d^*\leq 1$) and (ii) the development stage ($t_d^*>1$), where $t_d^*$ is the formation time defined by the duration of the deceleration stage. For starting jets with different $(L/D)_d$, the final circulation value and circulation growth rate of the SVR can be scaled by $[(L/D)_d]^{-0.5}$ and $[(L/D)_d]^{-1.5}$, respectively. Here $(L/D)_d$ represents the stroke ratio during the deceleration stage. Analysing the temporal evolution of fluid parcels in the vicinity of the nozzle exit reveals that SVR entrains fluid from both inside and outside of the nozzle. Additionally, the influence of the SVR on the leading vortex ring and the trailing jet has been examined, with particular attention to its effects on the propulsive performance of the starting jet. The SVR affects the profiles of axial velocity and gauge pressure at the nozzle exit, thereby enhancing the generation of total thrust during the deceleration stage. Analysis has shown that depending on the deceleration rate, SVR can enhance the average velocity thrust by at least $10\,\%$ and compensate for up to a $60\,\%$ reduction in pressure thrust due to deceleration.
Femtosecond oscillators with gigahertz (GHz) repetition rate are appealing sources for spectroscopic applications benefiting from the individually accessible and high-power comb line. The mode mismatch between the potent pump laser diode (LD) and the incredibly small laser cavity, however, limits the average output power of existing GHz Kerr-lens mode-locked (KLM) oscillators to tens of milliwatts. Here, we present a novel method that solves the difficulty and permits high average power LD-pumped KLM oscillators at GHz repetition rate. We propose a numerical simulation method to guide the realization of Kerr-lens mode-locking and comprehend the dynamics of the Kerr-lens mode-locking process. As a proof-of-principle demonstration, an LD-pumped Yb:KGW oscillator with up to 6.17-W average power and 184-fs pulse duration at 1.6-GHz repetition rate is conducted. The simulation had a good agreement with the experimental results. The cost-effective, compact and powerful laser source opens up new possibilities for research and industrial applications.
Emerging evidence has shown a strong correlation between serum triacylglycerol (TAG) levels, the inflammatory response, and Parkinson’s disease (PD) onset. However, the causal relationship between TAG levels and PD has not been well-established. We aimed to investigate the relationship between serum TAG levels and risk of PD and explore the potential mediating role of circulating immune cells and inflammatory proteins. We utilised genotype data from the GeneRISK cohort, and summary data from genome wide association studies investigating PD, circulating immune cells, inflammatory proteins, and plasma lipidomes. Using Mendelian randomization (MR) and multivariate MR (MVMR) analysis, we further adjusted for phosphatidylcholine (17:0_18:1) and triacylglycerol (58:7). Our results suggested a robust causal link between higher serum TAG (51:4) levels and a decreased risk of PD, with one standard deviation genetically instrumented higher serum TAG (51:4) level leading to a 21 percent [95% CI, 0.66 – 0.96] reduction in the risk of PD (p = 0.015). Additionally, the results of the mediation analysis suggested a possible role for mediation through circulating immune cells (including IgD-CD38-B cells and resting CD4 regulatory T cells), but not circulating inflammatory proteins, in the causal relationship between the plasma lipidomes and PD. Our study confirms a causal relationship between higher serum TAG (51:4) levels and a lower risk of PD and clarifies a possible role for mediation through circulating immune cells, but not inflammatory proteins. These findings indicate that serum triacylglycerol (51:4) regulates immunity to effectively lower the risk of PD.
Oncomelania hupensis (O. hupensis), the sole intermediate host of Schistosoma japonicum, greatly influence the prevalence and distribution of schistosomiasis japonica. The distribution area of O. hupensis has remained extensive for numerous years. This study aimed to establish a valid agent-based model of snail density and further explore the environmental conditions suitable for snail breeding. A marshland with O. hupensis was selected as a study site in Dongting Lake Region, and snail surveys were monthly conducted from 2007 to 2016. Combined with the data from historical literature, an agent-based model of snail density was constructed in NetLogo 6.2.0 and validated with the collected survey data. BehaviorSpace was used to identify the optimal ranges of soil temperature, pH, soil water content, and vegetation coverage for snail growth, development and reproduction. An agent-based model of snail density was constructed and showed a strong agreement with the monthly average snail density from the field surveys. As soil temperature increased, the snail density initially rose before declining, reaching its peak at around 21°C. There were similar variation patterns for other environmental factors. The findings from the model suggested that the optimum ranges of soil temperature, pH, soil water content and vegetation coverage were 19°C to 23 °C, 6.4 to 7.6, 42% to 75%, and 70% to 93%, respectively. A valid agent-based model of snail density was constructed, providing more objective information about the optimum ranges of environmental factors for snail growth, development and reproduction.
Coccidiosis is a parasitic disease caused by Eimeria spp., and the emergence of drug resistance has seriously affected the control of the disease. Using RNA-seq, we previously found that phosphoglycerate kinase of Eimeria tenella (EtPGK) was differentially downregulated in diclazuril-resistant (DZR) and maduramicin-resistant (MRR) strains compared with drug-sensitive (DS) strain. In this study, we further analysed the characteristics and functions of EtPGK to find the possible mechanism of drug resistance of E. tenella. Quantitative real-time PCR (qRT-PCR) and western blot found that EtPGK was highly expressed in sporulated oocysts, followed by sporozoites and second-generation merozoites of E. tenella. Indirect immunofluorescence localization showed that EtPGK was located mainly in the cytoplasm and on the surface of the parasites. Invasion inhibition assays showed that anti-rEtPGK antibody significantly inhibited the invasion of parasites. Further studies using qRT-PCR and western blot found that the transcription and translation levels of EtPGK were downregulated in both resistant (DZR and MRR) strains compared with the DS strain, and the transcription level correlated negatively with the drug concentration. The enzyme activity assay revealed that EtPGK enzyme activity was decreased in the DZR strain compared with the DS strain. qRT-PCR revealed that the mRNA transcription level of EtPGK was significantly downregulated in the field DZR strain and salinomycin-resistant strain compared with the DS strain. These results suggested that EtPGK has other important roles that are separate and distinct from its function in glycolysis, and it might be involved in the development of drug resistance of E. tenella.
The elasto-inertial focusing and rotating characteristics of spheroids in a square channel flow of Oldroyd-B viscoelastic fluids are studied by the direct forcing/fictitious domain method. The rotational behaviours, changes in the equilibrium positions and travel distances are explored to analyse the mechanisms of spheroid migration in viscoelastic fluids. Within the present simulated parameters (1 ≤ Re ≤ 100, 0 ≤ Wi ≤ 2, 0.4 ≤ α ≤3), the results show that there are four kinds of equilibrium positions and six (five) kinds of rotational behaviours for the elasto-inertial migration of prolate (oblate) spheroids. We are the first to identify a new rotational mode for the migration of prolate spheroids. Only when the particles are initially located at a corner and wall bisector, some special initial orientations of the spheroids have an impact on the final equilibrium position and rotational mode. In other general initial positions, the initial orientation of the spheroid has a negligible effect. A higher Weissenberg number means the faster the particles migrate to the equilibrium position. The spheroid gradually changes from the corner (CO), channel centreline (CC), diagonal line (DL) and cross-section midline (CSM) equilibrium positions as the elastic number decreases, depending on the aspect ratio, initial orientation and rotational behaviour of the particles and the elastic number of the fluid. When the elastic number is less than the critical value, the types of rotational modes of the spheroids are reduced. By controlling the elastic number near the critical value, spheroids with different aspect ratios can be efficiently separated.
Observational studies have shown a controversial relationship between dietary fat intake and Alzheimer's disease, and the causal effects are unclear.
Aims
To assess the causal effects of total fat, saturated fat and polyunsaturated fat (PUF) intakes on the risk of Alzheimer's disease.
Method
A two-sample Mendelian randomisation analysis was performed using genome-wide association study summary statistics on different types of fat intake from UK Biobank (n = 51 413) and on late-onset Alzheimer's disease (LOAD; 4282 cases, n = 307 112) and all forms of Alzheimer's disease (6281 cases, n = 309 154) from the FinnGen consortium. In addition, a multivariable Mendelian randomisation (MVMR) analysis was conducted to estimate the effects independent of carbohydrate and protein intakes.
Results
Genetically predicted per standard deviation increase in the total fat and saturated fat intakes were associated with 44 and 38% higher risks of LOAD (total fat: odds ratio = 1.44, 95% CI 1.03–2.02; saturated fat: odds ratio = 1.38, 95% CI 1.002–1.90; P = 0.049). The associations remained significant in the MVMR analysis (total fat: odds ratio = 3.31, 95% CI 1.74–6.29; saturated fat: odds ratio = 2.04, 95% CI 1.16–3.59). Total fat and saturated fat intakes were associated with a higher risk of all forms of Alzheimer's disease in the MVMR analysis (total fat: odds ratio = 2.09, 95% CI 1.22–3.57; saturated fat: odds ratio = 1.60, 95% CI 1.01–2.52). The PUF intake was not associated with LOAD or all forms of Alzheimer's disease.
Conclusions
This study indicated that total dietary fat intake, especially saturated fat, contributed to the risk of Alzheimer's disease, and the effects were independent of other nutrients. These findings informed prevention strategies and management for Alzheimer's disease directly towards reducing dietary saturated fat intake.
An experimental investigation is conducted to study the flow patterns, spectral properties and energy fluxes in thin-layer turbulence with varying system sizes and damping rates. It is found that although a system-size vortex (an indicator of spectral condensation) occurs for small system sizes and does not for large ones, the spectra for different system sizes consistently exhibit a scaling close to $k^{-3}$ in inverse cascade (another indicator of spectral condensation). On the other hand, under a fixed system size larger than the friction-dominated length scale, the energy spectrum in the inverse cascade range changes from $k^{-3}$ to $k^{-5/3}$ as the damping rate increases, suggesting that the friction-dominated length scale may not be a suitable parameter for predicting spectral transition. At lower damping rates and large system sizes, turbulent structures grow larger via inverse cascade, manifesting as long streamers, and the small-scale vortices are suppressed. This suppression leads to a reduction of energy flux at intermediate scales and a change in the spectral shape. The dimensionless Taylor microscale is found to exhibit a monotonic dependence on the damping rate. With the reduction in the damping rate, the Taylor microscale increases to become comparable with the forcing scale, and the spectrum in inverse cascade transits to a steeper scaling, $k^{-3}$, indicating that the dimensionless Taylor microscale may be used as a diagnostic parameter for spectral transition.
Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.
Objectives
This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.
Methods
We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.
Results
Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.
Conclusions
These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.
The occurrence of depression in adolescence, a critical period of brain development, linked with neuroanatomical and cognitive abnormalities. Neuroimaging studies have identified hippocampal abnormalities in those of adolescent patients. However, few studies have investigated the atypically developmental trends in hippocampal subfields in adolescents with depression and their relationships with cognitive dysfunctions.
Objectives
To explore the structural abnormalities of hippocampal subfields in patients with youth depression and examine how these abnormalities associated with cognitive deficits.
Methods
We included a sample of 79 first-episode depressive patients (17 males, age = 15.54±1.83) and 71 healthy controls (23 males, age = 16.18±2.85). The severity of these adolescent patients was assessed by depression scale, suicidal risk and self-harm behavior. Nine cognitive tasks were used to evaluate memory, cognitive control and attention abilities for all participants. Bilateral hippocampus were segmented into 12 subfields with T1 and T2 weighted images using Freesurfer v6.0. A mixed analysis of variance was performed to assess the differences in subfields volumes between all patients and controls, and between patients with mild and severe depression. Finally, LASSO regression was conducted to explore the associations between hippocampal subfields and cognitive abnormalities in patients.
Results
We found significant subfields atrophy in the CA1, CA2/3, CA4, dentate gyrus, hippocampal fissure, hippocampal tail and molecular layer subfields in patients. For those patients with severe depression, hippocampal subfields showed greater extensive atrophy than those in mild, particularly in CA1-4 subfields extending towards the subiculum. These results were similar across various severity assessments. Regression indicated that hippocampal subfields abnormalities had the strongest associations with memory dysfunction, and relatively week associations with cognitive control and attention. Notably, CA4 and dentate gyrus had the highest weights in the regression model.
Conclusions
As depressive severity increases, hippocampal subfield atrophy tends to spread from CA regions to surrounding areas, and primarily affects memory function in patients with youth depression. These results suggest hippocampus might be markers in progression of adolescent depression, offering new directions for early clinical intervention.