Neuropsychiatric Research Articles

The role of synbiotics in correcting gut microbiota disorders and increased intestinal permeability: A review

The gut microbiota participates in all metabolic processes in the human body, and its state determines the course of pathological processes. Intestinal infections, IBS, IBD, SIBO, diverticular disease, celiac disease, cancer, food intolerance, allergies, liver and pancreatic diseases, obesity, diabetes, metabolic syndrome, hematological, cardiological, genitourinary, rheumatological, neurological, neuropsychiatric and other disorders are associated with dysbiosis and increased permeability of the intestinal barrier. The means of correcting the gut microbiota are constantly being improved. The importance and expediency of using pro- and prebiotics as part of the complex therapy of many diseases is currently confirmed not only by large international clinical studies, but also by modern methods of diagnosing microbiota disorders. The review article presents clinically confirmed data on the effectiveness of the use of synbiotic Maxilac® for the correction of gut microbiota disorders and increased intestinal permeability in infectious diseases, postCOVID syndrome, IBS, including post-infectious IBS, as well as in severe atopic dermatitis in children.

Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions.

Mitochondria-endoplasmic reticulum contacts (MERCs) mediate a close and continuous communication between both organelles that is essential for the transfer of calcium and lipids to mitochondria, necessary for cellular signalling and metabolic pathways. Their structural and molecular characterisation has shown the involvement of many proteins that bridge the membranes of the two organelles and maintain the structural stability and function of these contacts. The crosstalk between the two organelles is fundamental for proper neuronal function and is now recognised as a component of many neurological disorders. In fact, an increasing proportion of MERC proteins take part in the molecular and cellular basis of pathologies affecting the nervous system. Here we review the alterations in MERCs that have been reported for these pathologies, from neurodevelopmental and neuropsychiatric disorders to neurodegenerative diseases. Although mitochondrial abnormalities in these debilitating conditions have been extensively attributed to the high energy demand of neurons, a distinct role for MERCs is emerging as a new field of research. Understanding the molecular details of such alterations may open the way to new paths of therapeutic intervention.

Fusing multi-scale functional connectivity patterns via Multi-Branch Vision Transformer (MB-ViT) for macaque brain age prediction

Brain age (BA) is defined as a measure of brain maturity and could help characterize both the typical brain development and neuropsychiatric disorders in mammals. Various biological phenotypes have been successfully applied to predict BA of human using chronological age (CA) as label. However, whether the BA of macaque, one of the most important animal models, can also be reliably predicted is largely unknown. To address this question, we propose a novel deep learning model called Multi-Branch Vision Transformer (MB-ViT) to fuse multi-scale (i.e., from coarse-grained to fine-grained) brain functional connectivity (FC) patterns derived from resting state functional magnetic resonance imaging (rs-fMRI) data to predict BA of macaques. The discriminative functional connections and the related brain regions contributing to the prediction are further identified based on Gradient-weighted Class Activation Mapping (Grad-CAM) method. Our proposed model successfully predicts BA of 450 normal rhesus macaques from the publicly available PRIMatE Data Exchange (PRIME-DE) dataset with lower mean absolute error (MAE) and mean square error (MSE) as well as higher Pearson's correlation coefficient (PCC) and coefficient of determination (R2) compared to other baseline models. The correlation between the predicted BA and CA reaches as high as 0.82 of our proposed method. Furthermore, our analysis reveals that the functional connections predominantly contributing to the prediction results are situated in the primary motor cortex (M1), visual cortex, area v23 in the posterior cingulate cortex, and dysgranular temporal pole. In summary, our proposed deep learning model provides an effective tool to accurately predict BA of primates (macaque in this study), and lays a solid foundation for future studies of age-related brain diseases in those animal models.

Microglial type I interferon signaling mediates chronic stress-induced synapse loss and social behavior deficits.

Inflammation and synapse loss have been associated with deficits in social behavior and are involved in pathophysiology of many neuropsychiatric disorders. Synapse loss, characterized by reduction in dendritic spines can significantly disrupt synaptic connectivity and neural circuitry underlying social behavior. Chronic stress is known to induce loss of spines and dendrites in the prefrontal cortex (PFC), a brain region implicated in social behavior. However, the underlying mechanisms are not well understood. In the present study, we investigated the role of type I Interferon (IFN-I) signaling in chronic unpredictable stress (CUS)-induced synapse loss and behavior deficits in mice. We found increased expression of type I IFN receptor (IFNAR) in microglia following CUS. Conditional knockout of microglial IFNAR in adult mice rescued CUS-induced social behavior deficits and synapse loss. Bulk RNA sequencing data show that microglial IFNAR deletion attenuated CUS-mediated changes in the expression of genes such as Keratin 20 (Krt20), Claudin-5 (Cldn5) and Nuclear Receptor Subfamily 4 Group A Member 1 (Nr4a1) in the PFC. Cldn5 and Nr4a1 are known for their roles in synaptic plasticity. Krt20 is an intermediate filament protein responsible for the structural integrity of epithelial cells. The reduction in Krt20 following CUS presents a novel insight into the potential contribution of cytokeratin in stress-induced alterations in neuroplasticity. Overall, these results suggest that microglial IFNAR plays a critical role in regulating synaptic plasticity and social behavior deficits associated with chronic stress conditions.

Recent Advances in representative small-molecule DRD2 inhibitors: Synthetic Routes and clinical applications

The dopamine D2 receptor (DRD2) represents a pivotal target for therapeutic intervention in the treatment of neuropsychiatric disorders, including schizophrenia, bipolar disorder, and Parkinson's disease. The successful discovery of numerous effective DRD2 inhibitors has led to their clinical application and ongoing evaluation in various clinical trials. This review explores the synthetic approaches and clinical applications of prototypical small-molecule DRD2 inhibitors that have received approval or are currently undergoing clinical trials, highlighting their therapeutic potential and challenges. The synthesis of these inhibitors employs various chemical strategies, including modifications of phenothiazine and butyrophenone structures, which have yielded significant antipsychotic agents like chlorpromazine and haloperidol. Additionally, newer classes of inhibitors, such as aripiprazole, exhibit partial agonist activity at DRD2, offering a unique therapeutic profile. Clinically, DRD2 inhibitors demonstrate efficacy in managing positive symptoms of schizophrenia, manic episodes in bipolar disorder, and dopaminergic imbalance in Parkinson's disease. However, the emergence of adverse effects, including tardive dyskinesia, extrapyramidal symptoms and metabolic syndrome, presents substantial challenges. Advances in the development of second-generation antipsychotics aim to balance efficacy with a better side effect profile by targeting additional neurotransmitter receptors. This review aims to deliver an overview of the synthesis and clinical applications of representative small-molecule DRD2 inhibitors across various clinical phases, thereby offering strategic insights for the advancement of DRD2 inhibitor development.

Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders.

Cyclic adenosine monophosphates (cAMP) and cyclic guanosine monophosphate (cGMP) are two essential second messengers, which are hydrolyzed by phosphodiesterase's (PDEs), such as PDE-2. Pharmacological inhibition of PDE-2 (PDE2A) in the central nervous system improves cAMP and cGMP signaling, which controls downstream proteins related to neuropsychiatric, neurodegenerative, and neurodevelopmental disorders. Considering that there are no specific treatments for these disorders, PDE-2 inhibitors' development has gained more attention in the recent decade. There is high demand for developing new-generation drugs targeting PDE2 for treating diseases in the central nervous and peripheral systems. This review summarizes the relationship between PDE-2 with neuropsychiatric, neurodegenerative, and neurodevelopmental disorders as well as its possible treatment, mainly involving inhibitors of PDE2.

Distorted time perception in patients with neurocognitive impairment

BackgroundTime perception is known to be distorted in patients with neuropsychiatric disorders. Therefore, this study aims to investigate the correlation between cognitive decline and time distortion by examining time perception in participants with neurocognitive impairment (Alzheimer's disease [AD], vascular dementia [VD], and Parkinson's disease dementia [PDD]) compared to those with subjective cognitive impairment (SCI). MethodsOverall, 569 participants with cognitive decline complaints between 2013 and 2022 were investigated. Participants were subjected to a verbal estimation task, time production task, time comparison task, and neuropsychological assessments. ResultsTime perception abilities were distorted in patients with neurocognitive impairment compared to those with SCI. Despite similar educational backgrounds, the vascular cognitive impairment (VCI)/VD group demonstrated the lowest MMSE scores (22.4 ± 4.2, p-value <0.001) and larger time-estimation errors. Patients with VCI/VD significantly underestimated time in the 35-s (19.6 ± 12.6s) and 60-s (28.7 ± 19.9s) tasks. In the time production task, patients with VCI/VD produced shorter times in their 15-s (12.7 ± 4.3; p-value = 0.001), 30-s (23.6 ± 8.3; p value < 0.001), and 60-s (43.8 ± 18.9; p-value <0.001) trials. In the time comparison task, the VCI/VD group had significantly fewer correct answers than that in the SCI groups (6.0 ± 1.3 vs. 7.1 ± 0.9, p-value <0.001). Correlation analysis revealed that multiple cognitive functions are involved in the time perception tasks. ConclusionsPatients with VCI/VD had the poorest time perception. These findings may provide a modest contribution to understanding the underlying pathophysiology and psychological connections related to temporal abilities in time perception.

Losing Control: Prefrontal Emotion Regulation Is Related to Symptom Severity and Predicts Treatment-Related Symptom Change in Adolescent Girls With Conduct Disorder

BackgroundEmotion regulation skills are linked to corticolimbic brain activity (e.g., dorsolateral prefrontal cortex [dlPFC] and limbic regions) and enable an individual to control their emotional experiences, thus allowing healthy social functioning. Disruptions in emotion regulation skills are reported in neuropsychiatric disorders, including conduct disorder or oppositional defiant disorder (CD/ODD). Clinically recognized means to ameliorate emotion regulation deficits observed in CD/ODD include cognitive or dialectical behavioral skills therapy as implemented in the START NOW program. However, the role of emotion regulation and its neural substrates in symptom severity and prognosis following treatment of adolescent CD/ODD has not been investigated. MethodsCross-sectional data including functional magnetic resonance imaging responses during emotion regulation (n = 114; average age = 15 years), repeated-measures assessments of symptom severity (pretreatment, posttreatment, long-term follow-up), and functional magnetic resonance imaging data collected prior to and following the START NOW randomized controlled trial (n = 44) for female adolescents with CD/ODD were analyzed using group comparisons and multiple regression. ResultsFirst, behavioral and neural correlates of emotion regulation were disrupted in female adolescents with CD/ODD. Second, ODD symptom severity was negatively associated with dlPFC/precentral gyrus activity during regulation. Third, treatment-related symptom changes were predicted by pretreatment ODD symptom severity and regulatory dlPFC/precentral activity. Additionally, pretreatment dlPFC/precentral activity and ODD symptom severity predicted long-term reductions in symptom severity following treatment for participants who received the START NOW treatment. ConclusionsOur findings demonstrate the important role that emotion regulation skills play in the characteristics of CD/ODD and show that regulatory dlPFC/precentral activity is positively associated with treatment response in female adolescents with CD/ODD.

Design, Synthesis, and Biological Evaluations of Novel Thiazolo[4,5-d]pyrimidine Corticotropin Releasing Factor (CRF) Receptor Antagonists as Potential Treatments for Stress Related Disorders and Congenital Adrenal Hyperplasia (CAH).

Corticotropin-releasing factor (CRF) is a key neuropeptide hormone that is secreted from the hypothalamus. It is the master hormone of the HPA axis, which orchestrates the physiological and behavioral responses to stress. Many disorders, including anxiety, depression, addiction relapse, and others, are related to over-activation of this system. Thus, new molecules that may interfere with CRF receptor binding may be of value to treat neuropsychiatric stress-related disorders. Also, CRF1R antagonists have recently emerged as potential treatment options for congenital adrenal hyperplasia. Previously, several series of CRF1 receptor antagonists were developed by our group. In continuation of our efforts in this direction, herein we report the synthesis and biological evaluation of a new series of CRF1R antagonists. Representative compounds were evaluated for their binding affinities compared to antalarmin. Four compounds (2, 5, 20, and 21) showed log IC50 values of -8.22, -7.95, -8.04, and -7.88, respectively, compared to -7.78 for antalarmin. This result indicates that these four compounds are superior to antalarmin by 2.5, 1.4, 1.7, and 1.25 times, respectively. It is worth mentioning that compound 2, in terms of IC50, is among the best CRF1R antagonists ever developed in the last 40 years. The in silico physicochemical properties of the lead compounds showed good drug-like properties. Thus, further research in this direction may lead to better and safer CRF receptor antagonists that may have clinical applications, particularly for stress-related disorders and the treatment of congenital adrenal hyperplasia.

Normative Modeling of Thalamic Nuclear Volumes and Characterization of Lateralized Volume Alterations in Alzheimer’s Disease Versus Schizophrenia

BackgroundThalamic nuclei facilitate a wide range of complex behaviors, emotions, and cognition and have been implicated in neuropsychiatric disorders including Alzheimer’s disease (AD) and schizophrenia (SCZ). The aim of this work was to establish novel normative models of thalamic nuclear volumes and their laterality indices and investigate their changes in SCZ and AD. MethodsVolumes of bilateral whole thalami and 10 thalamic nuclei were generated from T1 magnetic resonance imaging data using a state-of-the-art novel segmentation method in healthy control participants (n = 2374) and participants with early mild cognitive impairment (n = 211), late mild cognitive impairment (n = 113), AD (n = 88), and SCZ (n = 168). Normative models for each nucleus were generated from healthy control participants while controlling for sex, intracranial volume, and site. Extreme z-score deviations (|z| > 1.96) and z-score distributions were compared across phenotypes. z Scores were associated with clinical descriptors. ResultsIncreased infranormal and decreased supranormal z scores were observed in SCZ and AD. z Score shifts representing reduced volumes were observed in most nuclei in SCZ and AD, with strong overlap in the bilateral pulvinar, medial dorsal, and centromedian nuclei. Shifts were larger in AD, with evidence of a left-sided preference in early mild cognitive impairment while a predilection for right thalamic nuclei was observed in SCZ. The right medial dorsal nucleus was associated with disorganized thought and daily auditory verbal hallucinations. ConclusionsIn AD, thalamic nuclei are more severely and symmetrically affected while in SCZ, the right thalamic nuclei are more affected. We highlight the right medial dorsal nucleus, which may mediate multiple symptoms of SCZ and is affected early in the disease course.

Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer's disease.

Sporadic early-onset Alzheimer's disease (sEOAD) represents a significant but less-studied subtype of Alzheimer's disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.

Translational approaches to the neurobiological study of conditional discrimination and inhibition: Implications for psychiatric disease.

There is a growing number of studies investigating discriminatory fear conditioning and conditioned inhibition of fear to assess safety learning, in addition to extinction of cued fear. Despite all of these paradigms resulting in a reduction in fear expression, there are nuanced differences among them, which could be mediated through distinct behavioral and neural mechanisms. These differences could impact how we approach potential treatment options in clinical disorders with dysregulated fear responses. The objective of this review is to give an overview of the conditional discrimination and inhibition findings reported in both animal models and human neuropsychiatric disorders. Both behavioral and neural findings are reviewed among human and rodent studies that include conditional fear discrimination via conditional stimuli with and without reinforcement (CS+ vs. CS-, respectively) and/or conditional inhibition of fear through assessment of the fear response to a compound CS-/CS+ cue versus CS+. There are several parallels across species in behavioral fear expression as well as neural circuits promoting fear reduction in response to a CS- and/or CS-/CS+ compound cue. Continued and increased efforts to compare similar behavioral fear inhibition paradigms across species are needed to make breakthrough advances in our understanding and treatment approaches to individuals with fear disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The role of MRgFUS in the treatment of neuropsychiatric disorders: a state of the art.

Magnetic resonance-guided focused ultrasound (MRgFUS) is a contemporary non-invasive ablative procedure that utilizes high- or low-intensity ultrasound, guided and monitored by magnetic resonance imaging (MRI). While MRgFUS has been established as an effective treatment for conditions like essential tremor and tremor-dominant Parkinson's disease, it has recently emerged as a safe and promising ablative minimally invasive procedure for the management of treatment-resistant psychiatric disorders. Indeed, despite the availability of various pharmacological and behavioral therapies, a subset of psychiatric patients remains refractory to conventional treatments. To assess the feasibility and safety of MRgFUS in psychiatric disorders, a comprehensive literature search in PubMed and Scopus databases was conducted, resulting in the inclusion of five relevant articles in this review. While data on this innovative procedure are still limited, MRgFUS demonstrates potential as a safer and less invasive surgical technique for treating these disorders. Continued research efforts and data validation are imperative to establish MRgFUS as an additional, minimally invasive procedure for treatment-resistant psychiatric patients in the near future.

Chronic Stress Alters Synaptic Inhibition/Excitation Balance of Pyramidal Neurons But Not PV Interneurons in the Infralimbic and Prelimbic Cortices of C57BL/6J Mice.

The medial prefrontal cortex (mPFC) plays a pivotal role in regulating working memory, executive function, and self-regulatory behaviors. Dysfunction in the mPFC circuits is a characteristic feature of several neuropsychiatric disorders including schizophrenia, depression, and post-traumatic stress disorder. Chronic stress (CS) is widely recognized as a major triggering factor for the onset of these disorders. Although evidence suggests synaptic dysfunction in mPFC circuits following CS exposure, it remains unclear how different neuronal populations in the infralimbic (IL) and prelimbic (PL) cortices are affected in terms of synaptic inhibition/excitation balance (I/E ratio). Here, using neuroproteomic analysis and whole-cell patch-clamp recordings in pyramidal neurons (PNs) and parvalbumin (PV) interneurons within the PL and IL cortices, we examined the synaptic changes after 21 d of chronic unpredictable stress, in male mice. Our results reveal distinct impacts of CS on PL and IL PNs, resulting in an increased I/E ratio in both subregions but through different mechanisms: CS increases inhibitory synaptic drive in the PL while decreasing excitatory synaptic drive in the IL. Notably, the I/E ratio and excitatory and inhibitory synaptic drive of PV interneurons remained unaffected in both PL and IL circuits following CS exposure. These findings offer novel mechanistic insights into the influence of CS on mPFC circuits and support the hypothesis of stress-induced mPFC hypofunction.

The Identification of Potential Anti-Depression/Anxiety Drug Targets by Stress-Induced Rat Brain Regional Proteome and Network Analyses.

Depression and anxiety disorders are prevalent stress-related neuropsychiatric disorders and involve multiple molecular changes and dysfunctions across various brain regions. However, the specific and shared pathophysiological mechanisms occurring in these regions remain unclear. Previous research used a rat model of chronic mild stress (CMS) to segregate and identify depression-susceptible, anxiety-susceptible, and insusceptible groups; then the proteomes of six distinct brain regions (the hippocampus, prefrontal cortex, hypothalamus, pituitary, olfactory bulb, and striatum) were separately and quantitatively analyzed. To gain a comprehensive and systematic understanding of the molecular abnormalities, this study aimed to investigate and compare differential proteomics data from the six regions. Differentially expressed proteins (DEPs) were identified in between specific regions and across all regions and subjected to a series of bioinformatics analyses. Regional comparisons showed that stress-induced proteomic changes and corresponding gene ontology and pathway enrichments were largely distinct, attributable to differences in cell populations, protein compositions, and brain functions of these areas. Additionally, a notable degree of overlap in the significantly enriched terms was identified, potentially suggesting strong connections in the enrichment across different regions. Furthermore, intra-regional and inter-regional protein-protein interaction networks and drug-target-DEP networks were constructed. Integrated analysis of the three association networks in the six regions, along with the DisGeNET database, identified ten DEPs as potential targets for anti-depression/anxiety drugs. Collectively, these findings revealed commonalities and differences across different brain regions at the protein level induced by CMS, and identified several novel protein targets for the development of new therapeutics for depression and anxiety.

Clinical and molecular predictors of survival among atypical parkinsonian syndromes in a North African tertiary referral center

IntroductionAtypical Parkinsonian Syndromes(APS) are challenging neurodegenerative disorders due to their heterogeneous phenotypic overlaps.So far,there are no validated biomarkers that can accurately predict disease progression,and survival studies were highly different and contradictory. AimTo investigate clinical and molecular survival factors among Tunisian APS patients. MethodsA retrospective study included Tunisian APS-patients.Using clinical and molecular parameters,survival was explored by Kaplan-Meier analysis. ResultsWe included 409-APS patients divided into 166-DLB,112-PSP,81-MSA and 50-CBS.Survival rate was similar in synucleinopathies, while it differed in tauopathies,being shorter in PSP compared to CBS.Median survival in DLB was different according to gender(p = 0.0048),early parkinsonism and cognitive disorders. Among MSA, prognosis was worse in MSA-C-patients(p = 0.012) and those with stridor(p = 0.0049),oculomotor and neuropsychiatric disorders. For tauopathies, survival was shorter in PSP-RS(p = 0.027),cerebellar phenotype, those with tremor and swallowing problems at onset, early parkinsonism and memory impairment. For CBS,prognosis was worse in patients with tremor,swallowing and cognitive problems.Significant differences were noted in terms of survival across APS non-carriers of APOE-ε4(p < 0.001) as well APS patients carriers of MAPT-H1.PSP patients had lower survival rate according to MAPT haplotype carriage. Moreover, the number of copies had an influence as patients with H1/H2-MAPT profile had better prognosis than those with H1/H1. ConclusionThis study determined survival rates in APS subgroups,which were comparable across synucleinopathies but shorter in PSP and longer in CBS.It also characterized demographic,phenotypic,and genetic profiles identifying more aggressive forms within APS subgroups.These findings address clinical gaps,aiding counseling for patients and families and guiding clinical management.Furthermore,they could facilitate patient stratification in clinical trials where mortality is an outcome measure.

Enhancing the utility of tuberous sclerosis complex-associated neuropsychiatric disorders checklist in China.

The tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) Checklist is a reliable global screening tool for TAND in clinical settings, with six dimensions and 12 sections. For Chinese individuals with TSC, the implementation of the TAND Checklist provides a comprehensive approach to evaluating potential manifestations across various domains.

Application of Casein Micelles for Targeting Huntington's Disease in Experimental Zebrafish Model.

Huntington's disease (HD) is an incorrigible neuropsychiatric disorder with reduced cognition and motor abnormalities. Piperine (PIP) is an alkaloid with antioxidant, anti-inflammatory, and neuroprotective activities; however, poor therapeutic efficacy limits its further use. The current study focuses on the enhanced therapeutic potential of PIP@CM against an experimental zebrafish model of HD. PIP@CM was fabricated using spray drying technology, followed by solid-state investigations. We performed in vitro release and in vitro antioxidant activity (DPPH assay) of PIP and PIP@CMs. In addition, in vivo studies were conducted on zebrafish using 3-nitropropionic acid (3-NPA) (60mg/kg) as a neurotoxin and treated with PIP (5mg/kg) and PIP@CM (25mg/kg equivalent to 5mg/kg PIP). After dosing, various in vivo studies (behavioral, biochemical, and histological) were conducted. The solid-state characterization techniques revealed the loss of crystallinity after micelles formation. In vitro release and antioxidant assays showed higher release and enhanced activity of PIP@CM. In vivo studies revealed that 3-NPA administration causes HD, as evidenced by the results of open field test (OFT) and novel tank diving test (NTD) tests. Moreover, 3-NPA causes an increase in oxidative stress, as confirmed by biochemical and histopathological studies. PIP@CM treatment significantly improved behavioral performance in OFT and NTD tests and reduced oxidative stress markers as compared to pure PIP and untreated HD model.

The promise of precision functional mapping for neuroimaging in psychiatry.

Precision functional mapping (PFM) is a neuroimaging approach to reliably estimate metrics of brain function from individual people via the collection of large amounts of fMRI data (hours per person). This method has revealed much about the inter-individual variation of functional brain networks. While standard group-level studies, in which we average brain measures across groups of people, are important in understanding the generalizable neural underpinnings of neuropsychiatric disorders, many disorders are heterogeneous in nature. This heterogeneity often complicates clinical care, leading to patient uncertainty when considering prognosis or treatment options. We posit that PFM methods may help streamline clinical care in the future, fast-tracking the choice of personalized treatment that is most compatible with the individual. In this review, we provide a history of PFM studies, foundational results highlighting the benefits of PFM methods in the pursuit of an advanced understanding of individual differences in functional network organization, and possible avenues where PFM can contribute to clinical translation of neuroimaging research results in the way of personalized treatment in psychiatry.

Terapi &lt;i&gt;Montelukast &lt;/i&gt;pada Asma

Asthma is a chronic inflammatory respiratory condition caused by various inflammatory mediators, including those from the arachidonic acid pathway, which serves as a precursor for leukotrienes and prostaglandins. Leukotriene receptor antagonists (LTRAs) have been approved since 1998 as a treatment for asthma. Montelukast is one of the LTRAs that is useful for asthma control, including cases that accompanied by allergic rhinitis. A daily dose of 5-10 mg is recommended for persistent asthma as the preferred controller. LTRAs are not recommended for acute asthma exacerbation due to their relatively slow onset, but they are beneficial in preventing exacerbations. They are also indicated for exercise-induced asthma (EIA), and can be taken 2 hours prior to exercise. Montelukast can be administered as monotherapy or added to LABA-ICS therapy. It is suitable for adults, children, and infants over 1 year of age, preferably taken at night to prevent symptoms in the early morning. Possible side effects include respiratory tract infections, abdominal pain, diarrhea, and neuropsychiatric disorders. Montelukast is considered safe for use during pregnancy and breastfeeding. Physicians should provide comprehensive education for patients regarding medication compliance and the potential risks of side effects. Regular daily use of montelukast is beneficial in preventing acute exacerbations in asthma patients.