The neurostructural consequences of glaucoma and their overlap with disorders exhibiting emotional dysregulations: A voxel-based meta-analysis and tripartite system model.

BACKGROUND: Glaucoma, a progressive neurodegenerative disorder leading to irreversible blindness, is associated with heightened rates of generalized anxiety and depression. This study aims to comprehensively investigate brain morphological changes in glaucoma patients, extending beyond visual processing areas, and explores overlaps with morphological alterations observed in anxiety and depression. METHODS: A comparative meta-analysis was conducted, using case-control studies of brain structural integrity in glaucoma patients. We aimed to identify regions with gray matter volume (GMV) changes, examine their role within distinct large-scale networks, and assess overlap with alterations in generalized anxiety disorder (GAD) and major depressive disorder (MDD). RESULTS: Glaucoma patients exhibited significant GMV reductions in visual processing regions (lingual gyrus, thalamus). Notably, volumetric reductions extended beyond visual systems, encompassing the left putamen and insula. Behavioral and functional network decoding revealed distinct large-scale networks, implicating visual, motivational, and affective domains. The insular region, linked to pain and affective processes, displayed reductions overlapping with alterations observed in GAD. LIMITATIONS: While the study identified significant morphological alterations, the number of studies from both the glaucoma and GAD cohorts remains limited due to the lack of independent studies meeting our inclusion criteria. CONCLUSION: The study proposes a tripartite brain model for glaucoma, with visual processing changes related to the lingual gyrus and additional alterations in the putamen and insular regions tied to emotional or motivational functions. These neuroanatomical changes extend beyond the visual system, implying broader implications for brain structure and potential pathological developments, providing insights into the overall neurological consequences of glaucoma.

Exploring volumetric abnormalities in subcortical L-HPA axis structures in pediatric generalized anxiety disorder.

BACKGROUND: Pediatric generalized anxiety disorder (GAD) is debilitating and increasingly prevalent, yet its etiology remains unclear. Some believe the disorder to be propagated by chronic dysregulation of the limbic-hypothalamic-pituitary-adrenal (L-HPA) axis, but morphometric studies of implicated subcortical areas have been largely inconclusive. Recognizing that certain subcortical subdivisions are more directly involved in L-HPA axis functioning, this study aims to detect specific abnormalities in these critical areas. METHODS: Thirty-eight MRI scans of preschool children with (n = 15) and without (n = 23) GAD underwent segmentation and between-group volumetric comparisons of the basolateral amygdala (BLA), ventral hippocampal subiculum (vSC), and mediodorsal medial magnocellular (MDm) area of the thalamus. RESULTS: Children with GAD displayed significantly larger vSC compared to healthy peers, F(1, 31) = 6.50, pFDR = .048. On average, children with GAD presented with larger BLA and MDm, Fs(1, 31) ≥ 4.86, psFDR ≤ .054. Exploratory analyses revealed right-hemispheric lateralization of all measures, most notably the MDm, F(1, 31) = 8.13, pFDR = .024, the size of which scaled with symptom severity, r = .83, pFDR = .033. CONCLUSION: The BLA, vSC, and MDm are believed to be involved in the regulation of anxiety and stress, both individually and collectively through the excitation and inhibition of the L-HPA axis. All were found to be enlarged in children with GAD, perhaps reflecting hypertrophy related to hyperexcitability, or early neuronal overgrowth. Longitudinal studies should investigate the relationship between these early morphological differences and the long-term subcortical atrophy previously observed.

Grey matter alterations in generalized anxiety disorder: A voxel-wise meta-analysis of voxel-based morphometry studies.

OBJECTIVE: Grey matter, a crucial component of the brain, has been found altered in generalized anxiety disorder (GAD) of several voxel-based morphometry studies. The conclusive and consistent grey matter alterations in GAD have not been confirmed. METHOD: Eleven voxel-based morphometry studies of GAD patients were included in the current systematic review and meta-analysis. The linear model of anxiety severity scores was applied to explore the relationship of grey matter alterations and anxiety severity. The subgroup analysis of adult GAD and adolescent GAD was also performed. RESULTS: Significantly modest grey matter alterations in the left superior temporal gyrus of patients with GAD were found. The anxiety severity score was significantly correlated with grey matter alterations in the right insula, lenticular nucleus, putamen and striatum. The subgroup analysis of adult GAD and adolescent GAD all failed to show significant grey matter alterations. However, in the adult GAD subgroup, anxiety severity score was significantly correlated with grey matter alterations in the right insula. CONCLUSION: GAD might have the modest grey matter alterations in the left superior temporal gyrus. Anxiety severity might be related to the grey matter alterations in the limbic regions, such as the right insula, lenticular nucleus, putamen and striatum. This kind of correlation might be related to the effects of adult GAD. Future studies with adequate sample sizes and sophisticated GAD categories will be needed.

The difference in volumetric alternations of the orbitofrontal-limbic-striatal system between major depressive disorder and anxiety disorders: A systematic review and voxel-based meta-analysis.

BACKGROUND: Major depressive disorder (MDD) and anxiety disorders (ANX) are psychiatric disorders with high mutual comorbidity rates that might indicate some shared neurobiological pathways between them, but they retain diverse phenotypes that characterize themselves specifically. However, no consistent evidence exists for common and disorder-specific gray matter volume (GMV) alternations between them. METHODS: A systematic review and meta-analysis on voxel-based morphometry studies of patients with MDD and ANX were performed. The effect of comorbidity was explicitly controlled during disorder-specific analysis and particularly investigated in patient with comorbidity. RESULTS: A total of 45 studies with 54 datasets comprising 2196 patients and 2055 healthy participants met the inclusion criteria. Deficits in the orbitofrontal cortex, striatum, and limbic regions were found in MDD and ANX. The disorder-specific analyses showed decreased GMV in the bilateral anterior cingulate cortex, right striatum, hippocampus, and cerebellum in MDD, while decreased GMV in the left striatum, amygdala, insula, and increased cerebellar volume in ANX. A totally different GMV alternation pattern was shown involving bilateral temporal and parietal gyri and left fusiform gyrus in patients with comorbidity. LIMITATIONS: Owing to the design of included studies, only partial patients in the comorbid group had a secondary comorbidity diagnosis. CONCLUSION: Patients with MDD and ANX shared a structural disruption in the orbitofrontal-limbic-striatal system. The disorder-specific effects manifested their greatest severity in distinct lateralization and directionality of these changes that differentiate MDD from ANX. The comorbid group showed a totally different GMV alternation pattern, possibly suggesting another illness subtype that requires further investigation.

Grey matter structural alterations in anxiety disorders: a voxel-based meta-analysis.

Anxiety disorders (ADs) are a group of prevalent and destructive mental illnesses, but the current understanding of their underlying neuropathology is still unclear. Employing voxel-based morphometry (VBM), previous studies have demonstrated several common brain regions showing grey matter volume (GMV) abnormalities. However, contradictory results have been reported among these studies. Considering that different subtypes of ADs exhibit common core symptoms despite different diagnostic criteria, and previous meta-analyses have found common core GMV-altered brain regions in ADs, the present research aimed to combine the results of individual studies to identify common GMV abnormalities in ADs. Therefore, we first performed a systematic search in PubMed, Embase, and Web of Science on studies investigating GMV differences between patients with ADs and healthy controls (HCs). Then, the anisotropic effect-size signed differential mapping (AES-SDM) was applied in this meta-analysis. A total of 24 studies (including 25 data sets) were included in the current study, and 906 patients with ADs and 1003 HCs were included. Compared with the HCs, the patients with ADs showed increased GMV in the left superior parietal gyrus, right angular gyrus, left precentral gyrus, and right lingual gyrus, and decreased GMV in the bilateral insula, bilateral thalamus, left caudate, and right putamen. In conclusion, the current study has identified some abnormal GMV brain regions that are related to the pathological mechanisms of anxiety disorders. These findings could contribute to a better understanding of the underlying neuropathology of ADs.

The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review.

BACKGROUND: Depression and anxiety are the most common mental disorders worldwide. OBJECTIVE: We aimed to review silymarin and silibinin effects and underlying mechanisms in the central nervous system (CNS) for depression and anxiety treatment. METHODS: The research protocol was prepared based on following the PRISMA statement. An extensive search was done in essential databases such as PubMed, Cochrane Library, Web of Science (ISI), Embase, and Scopus. Considering the study inclusion and exclusion criteria, 17 studies were finally included. The desired information was extracted from the studies and recorded in Excel, and the consequences and mechanisms were reviewed. RESULTS: Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus. They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels. Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. In addition, silymarin and silibinin reduced interleukin (IL)-6, IL-1ß, and IL-12ß, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation. CONCLUSION: Silymarin and silibinin exert anti-depression and anxiolytic effects by regulating neurotransmitters, endocrine, neurogenesis, and immunologic systems. Therefore, as natural and complementary medicines, they can be used to reduce the symptoms of depression and anxiety; However, more clinical studies are needed in this field.

Brain morphometry points to emerging patterns of psychosis, depression, and anxiety vulnerability over a 2-year period in childhood.

BACKGROUND: Gray matter morphometry studies have lent seminal insights into the etiology of mental illness. Existing research has primarily focused on adults and then, typically on a single disorder. Examining brain characteristics in late childhood, when the brain is preparing to undergo significant adolescent reorganization and various forms of serious psychopathology are just first emerging, may allow for a unique and highly important perspective of overlapping and unique pathogenesis. METHODS: A total of 8645 youth were recruited as part of the Adolescent Brain and Cognitive Development study. Magnetic resonance imaging scans were collected, and psychotic-like experiences (PLEs), depressive, and anxiety symptoms were assessed three times over a 2-year period. Cortical thickness, surface area, and subcortical volume were used to predict baseline symptomatology and symptom progression over time. RESULTS: Some features could possibly signal common vulnerability, predicting progression across forms of psychopathology (e.g. superior frontal and middle temporal regions). However, there was a specific predictive value for emerging PLEs (lateral occipital and precentral thickness), anxiety (parietal thickness/area and cingulate), and depression (e.g. parahippocampal and inferior temporal). CONCLUSION: Findings indicate common and distinct patterns of vulnerability for varying forms of psychopathology are present during late childhood, before the adolescent reorganization, and have direct relevance for informing novel conceptual models along with early prevention and intervention efforts.

Adolescent intermittent ethanol exposure enhances adult stress effects in male rats.

Binge patterns of alcohol use, prevalent among adolescents, are associated with a higher probability of developing alcohol use disorders (AUD) and other psychiatric disorders, like anxiety and depression. Additionally, adverse life events strongly predict AUD and other psychiatric disorders. As such, the combined fields of stress and AUD have been well established, and animal models indicate that both binge-like alcohol exposure and stress exposure elevate anxiety-like behaviors. However, few have investigated the interaction of adolescent intermittent ethanol (AIE) and adult stressors. We hypothesized that AIE would increase vulnerability to restraint-induced stress (RS), manifested as increased anxiety-like behavior. After AIE exposure, in adulthood, animals were tested on forced swim (FST) and saccharin preference (SP) and then exposed to either RS (90 min/5 days) or home-cage control. Twenty-four hours after the last RS session, animals began testing on the elevated plus maze (EPM), and were re-tested on FST and SP. A separate group of animals were sacrificed in adulthood after AIE and RS, and brains were harvested for immunoblot analysis of dorsal and ventral hippocampus. Consistent with previous reports, AIE had no significant effect on closed arm time in the EPM (anxiety-like behavior). However, in male rats the interaction of AIE and adult RS increased time spent in the closed arms. No effect was observed among female animals. AIE and RS-specific alterations were found in glial and synaptic markers (GLT-1, FMRP and PSD-95) in male animals. These findings indicate AIE has sex-specific effects on both SP and the interaction of AIE and adult RS, which induces a propensity toward anxiety-like behavior in males. Also, AIE produces persistent hippocampal deficits that may interact with adult RS to cause increased anxiety-like behaviors. Understanding the mechanisms behind this AIE-induced increase in stress vulnerability may provide insight into treatment and prevention strategies for alcohol use disorders.

Higher polygenic risk scores for anxiety disorders are associated with reduced area in the anterior cingulate gyrus.

Anxiety disorders are heterogeneous, show a moderate genetic contribution and are associated with inconsistent cortical structure alterations. Here, we investigated whether genetic factors for anxiety disorders contribute to cortical alterations by conducting polygenic risk score (PRS) analyses. We calculated PRSs for anxiety disorders at several P value thresholds (from PT ≤ 5.0 × 10-8 to PT ≤ 1.0) based on the latest large-scale genome-wide association study of anxiety disorders from the UK biobank (25,453 cases; 58,113 controls) in an independent sample of psychiatrically and physically healthy subjects (n = 174). Using regression after adjusting for confounding factors, we tested whether these PRSs were associated with the surface area and cortical thickness in 34 bilateral brain regions extracted using FreeSurfer. A higher PRS for anxiety disorders at PT ≤ 1.0 was significantly associated with a reduced right caudal anterior cingulate area (beta = -0.25, puncorrected = 9.51 × 10-4, pcorrected = 0.032). PRSs based on more common SNPs, especially from PT ≤ 0.01 to PT ≤ 1.0, were associated with the right caudal anterior cingulate area (a maximum at PT ≤ 0.5: R2 = 0.066, beta = -0.27, puncorr = 3.81 × 10-4, pcorr = 0.013). Furthermore, individuals in the highest quartile for anxiety disorder PRS had lower surface area and volume in the right anterior cingulate gyrus than those in the lowest quartile. We suggest a shared genetic etiology between anxiety disorders and structural features of the anterior cingulate gyrus, possibly contributing to the pathogenesis of anxiety disorders via emotional dysregulations. Our findings suggest the potential usefulness of PRS to reduce pathological heterogeneity among anxiety disorders.

Neonatal inflammation via persistent TGF-ß1 downregulation decreases GABAAR expression in basolateral amygdala leading to the imbalance of the local excitation-inhibition circuits and anxiety-like phenotype in adult mice.

Neonatal inflammation can increase the risk of anxiety disorder in adulthood. The balance between glutamatergic excitatory and GABAergic inhibitory transmissions in the basolateral amygdala (BLA) plays a vital role in controlling anxiety state. Based on the reports that early-life inflammation had adverse effects on GABAergic system, the aim of this study was to investigate whether and how neonatal inflammation affects excitatory-inhibitory circuits in the BLA resulting in anxiety disorder. Neonatal mice received a daily subcutaneous injection of lipopolysaccharide (LPS, 50 µg/kg) or saline on postnatal days 3-5. LPS-treated mice developed anxiety behaviors accompanied by the hyperactivity of adrenal axis in adulthood. Electrophysiological study revealed the increase of postsynaptic neuronal excitability in the cortical-BLA excitatory synapses of LPS mice which could be recovered by bath-application of GABAAR agonist suggesting the impairment of GABAergic system in LPS mice. Compared with controls, GABAARα2 subunit expression and density of GABA-evoked current in BLA principal neurons were reduced in LPS mice. Additionally, neonatal LPS treatment resulted in the down-regulation of transforming growth factor-beta 1 (TGF-ß1) expression and PKC signaling pathway in the adult BLA. The local TGF-ß1 overexpression in the BLA improved GABAARα2 expression via up-regulating the activity of PKC signaling, which corrected GABAAR-mediated inhibition leading to the abolishment of anxiety-like change in adrenal axis regulation and behaviors in LPS mice. These data suggest the persistent TGF-ß1deficit induces the down-regulation of GABAARα2 expression and subsequent disruption of the excitation-inhibition balance in the BLA circuits, which is the important mechanisms of neonatal inflammation-induced anxiety disorder.

Depressive symptoms reduce when dorsolateral prefrontal cortex-precuneus connectivity normalizes after functional connectivity neurofeedback.

Depressive disorders contribute heavily to global disease burden; This is possibly because patients are often treated homogeneously, despite having heterogeneous symptoms with differing underlying neural mechanisms. A novel treatment that can directly influence the neural circuit relevant to an individual patient's subset of symptoms might more precisely and thus effectively aid in the alleviation of their specific symptoms. We tested this hypothesis in a proof-of-concept study using fMRI functional connectivity neurofeedback. We targeted connectivity between the left dorsolateral prefrontal cortex/middle frontal gyrus and the left precuneus/posterior cingulate cortex, because this connection has been well-established as relating to a specific subset of depressive symptoms. Specifically, this connectivity has been shown in a data-driven manner to be less anticorrelated in patients with melancholic depression than in healthy controls. Furthermore, a posterior cingulate dominant state-which results in a loss of this anticorrelation-is expected to specifically relate to an increase in rumination symptoms such as brooding. In line with predictions, we found that, with neurofeedback training, the more a participant normalized this connectivity (restored the anticorrelation), the more related (depressive and brooding symptoms), but not unrelated (trait anxiety), symptoms were reduced. Because these results look promising, this paradigm next needs to be examined with a greater sample size and with better controls. Nonetheless, here we provide preliminary evidence for a correlation between the normalization of a neural network and a reduction in related symptoms. Showing their reproducibility, these results were found in two experiments that took place several years apart by different experimenters. Indicative of its potential clinical utility, effects of this treatment remained one-two months later.Clinical trial registration: Both experiments reported here were registered clinical trials (UMIN000015249, jRCTs052180169).

Association between depression and anxiety on symptom and function after surgery for lumbar spinal stenosis.

Evidence on the role of depression and anxiety in patients undergoing surgical treatment for symptomatic degenerative lumbar spinal stenosis (DLSS) is conflicting. We aimed to assess the association between depression and anxiety with symptoms and function in patients undergoing surgery for DLSS. Included were patients with symptomatic DLSS participating in a prospective multicentre cohort study who underwent surgery and completed the 24-month follow-up. We used the hospital anxiety and depression scale (HADS) to assess depression/anxiety. We used mixed-effects models to quantify the impact on the primary outcome change in the spinal stenosis measure (SSM) symptoms/function subscale from baseline to 12- and 24-months. Logistic regression analysis was used to quantify the odds of the SSM to reach a minimal clinically important difference (MCID) at 24 months follow-up. The robustness of the results in the presence of unmeasured confounding was quantified using a benchmarking method based on a multiple linear model. Out of 401 patients 72 (17.95%) were depressed and 80 anxious (19.05%). Depression was associated with more symptoms (ß = 0.36, 95% confidence interval (CI) 0.20 to 0.51, p < 0.001) and worse function (ß = 0.37, 95% CI 0.24 to 0.50, p < 0.001) at 12- and 24-months. Only the association between baseline depression and SSM symptoms/function was robust at 12 and 24 months. There was no evidence for baseline depression/anxiety decreasing odds for a MCID in SSM symptoms and function over time. In patients undergoing surgery for symptomatic DLSS, preoperative depression but not anxiety was associated with more severe symptoms and disability at 12 and 24 months.

ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders.

Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA-Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA-Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA-Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.

Topoisomerase IIIß Deficiency Induces Neuro-Behavioral Changes and Brain Connectivity Alterations in Mice.

Topoisomerase IIIß (Top3ß), the only dual-activity topoisomerase in mammals that can change topology of both DNA and RNA, is known to be associated with neurodevelopment and mental dysfunction in humans. However, there is no report showing clear associations of Top3ß with neuropsychiatric phenotypes in mice. Here, we investigated the effect of Top3ß on neuro-behavior using newly generated Top3ß deficient (Top3ß-/-) mice. We found that Top3ß-/- mice showed decreased anxiety and depression-like behaviors. The lack of Top3ß was also associated with changes in circadian rhythm. In addition, a clear expression of Top3ß was demonstrated in the central nervous system of mice. Positron emission tomography/computed tomography (PET/CT) analysis revealed significantly altered connectivity between many brain regions in Top3ß-/- mice, including the connectivity between the olfactory bulb and the cerebellum, the connectivity between the amygdala and the olfactory bulb, and the connectivity between the globus pallidus and the optic nerve. These connectivity alterations in brain regions are known to be linked to neurodevelopmental as well as psychiatric and behavioral disorders in humans. Therefore, we conclude that Top3ß is essential for normal brain function and behavior in mice and that Top3ß could be an interesting target to study neuropsychiatric disorders in humans.

Mindfulness augmentation for anxiety through concurrent use of transcranial direct current stimulation: a randomized double-blind study.

Transcranial direct current stimulation (tDCS) have revealed the capability to augment various types of behavioural interventions. We aimed to augment the effects of mindfulness, suggested for reducing anxiety, with concurrent use of tDCS. We conducted a double-blind randomized study with 58 healthy individuals. We introduced treadmill walking for focused meditation and active or sham tDCS on the left dorsolateral prefrontal cortex for 20 min. We evaluated outcomes using State-Trait Anxiety Inventory-State Anxiety (STAI) before the intervention as well as immediately, 60 min, and 1 week after the intervention, and current density from electroencephalograms (EEG) before and after the intervention. The linear mixed-effect models demonstrated that STAI-state anxiety showed a significant interaction effect between 1 week after the intervention and tDCS groups. As for alpha-band EEG activity, the current density in the rostral anterior cingulate cortex (rACC) was significantly reduced in the active compared with the sham stimulation group, and a significant correlation was seen between changes in STAI-trait anxiety and the current density of the rACC in the active stimulation group. Our study provided that despite this being a one-shot and short intervention, the reduction in anxiety lasts for one week, and EEG could potentially help predict its anxiolytic effect.

Prevalence and predictors of depression, anxiety, and stress among adults in Ghana: A community-based cross-sectional study.

INTRODUCTION: Over the past two decades, there have been several global interventions including the Sustainable Development Goals (SDGs), aimed at improving health outcomes. Despite efforts by countries to achieve the SDG targets, mental health challenges remain major public health concerns globally. We examined the prevalence and predictors of depression, anxiety, and stress as well as the comorbidities of these mental health issues among adults. MATERIALS AND METHODS: This was a community-based cross-sectional study conducted among 2456 adults in four districts of the Volta Region of Ghana using data from the UHAS-Yonsei University Partnership Project. We analysed the data using frequency, percentage, mean, standard deviation, correlation, and binary logistic regression. RESULTS: Overall, 51.8% of the participants had at least one of the mental health issues examined. The prevalence of a mental health issue was 25.2%, 53.3%, and 9.7% for depression, anxiety, and stress respectively. Participants constituting 8.3% experienced all three mental health issues as comorbidities. Participants' level of formal education and income significantly predicted depression, anxiety, and stress respectively at the multivariable level. Adults with a tertiary level of education were, for instance, 68% (AOR = 0.32, 95%CI = 0.15-0.66), 65% (AOR = 0.35, 95%CI = 0.17-0.73), and 50% (AOR = 0.50, 95%CI = 0.33-0.76) less likely to experience depression, anxiety, and stress, respectively compared with those who had no formal education. CONCLUSION: The majority of our study participants either experienced depression, anxiety, or stress. There were quite high comorbidities of the mental health issues among the adult population. To accelerate progress towards the achievement of SDG 3.4 target of promoting mental health and wellbeing for all by the year 2030, there is a need for effective implementation of the country's 2012 Mental Health Act which makes provisions for the establishment of a Mental Health Fund. This could improve the financial circumstances of indigenes as income has been realised in the present study as an important factor influencing depression, anxiety, and stress among the adult population.

Evaluation of Effect of Curcumin on Psychological State of Patients with Pulmonary Hypertension by Magnetic Resonance Image under Deep Learning.

This research aimed to evaluate the right ventricular segmentation ability of magnetic resonance imaging (MRI) images based on deep learning and evaluate the influence of curcumin (Cur) on the psychological state of patients with pulmonary hypertension (PH). The heart MRI images were detected based on the You Only Look Once (YOLO) algorithm, and then the MRI image right ventricle segmentation algorithm was established based on the convolutional neural network (CNN) algorithm. The segmentation effect of the right ventricle in cardiac MRI images was evaluated regarding intersection-over-union (IOU), Dice coefficient, accuracy, and Jaccard coefficient. 30 cases of PH patients were taken as the research object. According to different treatments, they were rolled into control group (conventional treatment) and Cur group (conventional treatment + Cur), with 15 cases in each group. Changes in the scores of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) of the two groups of patients before and after treatment were analyzed. It was found that the average IOU of the heart target detection frame of the MRI image and the true bounding box before correction was 0.7023, and the IOU after correction was 0.9016. The Loss of the MRI image processed by the CNN algorithm was 0.05, which was greatly smaller than those processed by other algorithms. The Dice coefficient, Jaccard coefficient, and accuracy of the MRI image processed by CNN were 0.89, 0.881, and 0.994, respectively. The MRI images of PH patients showed that the anterior wall of the right ventricle was notably thickened, and the main pulmonary artery was greatly widened. After treatment, the SAR and SDS scores of the two groups were lower than those before treatment (P < 0.05), and the SAR and SDS scores of the curcumin group were lower than those of the control group (P < 0.05). To sum up, the right ventricular segmentation ability of MRI images based on deep learning was improved, and Cur can remarkably alleviate the psychological state of PH patients, which provided a reference for the diagnosis and treatment for PH patients.

Functional limitations in people with multimorbidity and the association with mental health conditions: Baseline data from the Canadian Longitudinal Study on Aging (CLSA).

INTRODUCTION: Increasing multimorbidity is often associated with declining physical functioning, with some studies showing a disproportionate impact on functioning when mental health conditions are present. More research is needed because most multimorbidity studies exclude mental health conditions. OBJECTIVES: This study aims to improve our understanding of the association between functional limitation and multimorbidity, including a comparison of those with multimorbidity that includes versus excludes mental health conditions. METHODS: This is a population-based, cross-sectional analysis of data from The Canadian Longitudinal Study on Aging. Functional limitation was defined as the presence of any of 14 activities of daily living (ADLs) or instrumental activities of daily living (IADLs). Multimorbidity, measured by the number of chronic conditions, included mood and anxiety disorders. Logistic regression explored the association between multimorbidity (with and without mental health conditions) and functional limitation. Factor analysis identified common condition clusters to help understand clinical complexity in those with mood/anxiety disorders and the potential influences on functional limitation. RESULTS: There were 51,338 participants, with a similar proportion of men and women (49% versus 51%) and 42% age 65 years or older. Fifteen percent (15%) had no chronic conditions and 17% had 5+. Ten percent (10%) reported at least one ADL or IADL limitation. Odds ratios (ORs) for functional limitation increased with multimorbidity and were generally higher for those with versus without mental health conditions (e.g., ORs from 1 to 5+ chronic conditions increased 1.9 to 15.8 for those with mood/anxiety disorders versus 1.8 to 10.2 for those without). Factor analysis showed that mood/anxiety conditions clustered with somatic conditions (e.g., migraines, bowel/gastrointestinal disorders). CONCLUSION: This study found higher odds of functional limitation for those with multimorbidity that included versus excluded mental health conditions, at all levels of multimorbidity. It highlights the need for concurrent management of mental and physical comorbidities to prevent functional limitations and future decline. This approach is aligned with the NICE clinical assessment and management guidelines for people with multimorbidity.

Paternal exposure to excessive methionine altered behavior and neurochemical activities in zebrafish offspring.

An increase in plasma L-methionine (Met) levels, even if transitory, can cause important toxicological alterations in the affected individuals. Met is essential in the regulation of epigenetic mechanisms and its influence on the subsequent generation has been investigated. However, few studies have explored the influence of a temporary increase in Met levels in parents on their offspring. This study evaluated the behavioral and neurochemical effects of parental exposure to high Met concentration (3 mM) in zebrafish offspring. Adult zebrafish were exposed to Met for 7 days, maintained for additional 7 days in tanks that contained only water, and then used for breeding. The offspring obtained from these fish (F1) were tested in this study. During the early stages of offspring development, morphology, heart rate, survival, locomotion, and anxiety-like behavior were assessed. When these animals reached the adult stage, locomotion, anxiety, aggression, social interaction, memory, oxidative stress, and levels of amino acids and neurotransmitters were analyzed. F1 larvae Met group presented an increase in the distance and mean speed when compared to the control group. F1 adult Met group showed decreased anxiety-like behavior and locomotion. An increase in reactive oxygen species was also observed in the F1 adult Met group whereas lipid peroxidation and antioxidant enzymes did not change when compared to the control group. Dopamine, serotonin, glutamate, and glutathione levels were increased in the F1 adult Met group. Taken together, our data show that even a transient increase in Met in parents can cause behavioral and neurochemical changes in the offspring, promoting transgenerational effects.

BDNF Overexpression in the Ventral Hippocampus Promotes Antidepressant- and Anxiolytic-Like Activity in Serotonin Transporter Knockout Rats.

BDNF plays a pivotal role in neuroplasticity events, vulnerability and resilience to stress-related disorders, being decreased in depressive patients and increased after antidepressant treatment. BDNF was found to be reduced in patients carrying the human polymorphism in the serotonin transporter promoter region (5-HTTLPR). The serotonin knockout rat (SERT-/-) is one of the animal models used to investigate the underlying molecular mechanisms of depression in humans. They present decreased BDNF levels, and anxiety- and depression-like behavior. To investigate whether upregulating BDNF would ameliorate the phenotype of SERT-/- rats, we overexpressed BDNF locally into the ventral hippocampus and submitted the animals to behavioral testing. The results showed that BDNF overexpression in the vHIP of SERT-/- rats promoted higher sucrose preference and sucrose intake; on the first day of the sucrose consumption test it decreased immobility time in the forced swim test and increased the time spent in the center of a novel environment. Furthermore, BDNF overexpression altered social behavior in SERT-/- rats, which presented increased passive contact with test partner and decreased solitary behavior. Finally, it promoted decrease in plasma corticosterone levels 60 min after restraint stress. In conclusion, modulation of BDNF IV levels in the vHIP of SERT-/- rats led to a positive behavioral outcome placing BDNF upregulation in the vHIP as a potential target to new therapeutic approaches to improve depressive symptoms.