Anti-herpetic tau preserves neurons via the cGAS-STING-TBK1 pathway in Alzheimer's disease.

Alzheimer's disease (AD) diagnosis relies on the presence of extracellular β-amyloid (Aβ) and intracellular hyperphosphorylated tau (p-tau). Emerging evidence suggests a potential link between AD pathologies and infectious agents, with herpes simplex virus 1 (HSV-1) being a leading candidate. Our investigation, using metagenomics, mass spectrometry, western blotting, and decrowding expansion pathology, detects HSV-1-associated proteins in human brain samples.

Depression is Associated with Treatment Response Trajectories in Adults with Prolonged Grief Disorder: A Machine Learning Analysis.

Unlabelled: Although evidence-based treatments for Prolonged Grief Disorder (PGD) exist, pretreatment characteristics associated with differential improvement trajectories have not been identified. To identify clinical factors relevant to optimizing PGD treatment outcomes, we used unsupervised and supervised machine learning to study treatment effects from a double-blinded, placebo-controlled, randomized clinical trial. Participants were randomized into four treatment groups for 20 weeks: citalopram with grief-informed clinical management, citalopram with prolonged grief disorder therapy (PGDT), pill placebo with PGDT, or pill placebo with clinical management.

Psychological Assessment and Intervention at the Boston Marathon.

The Boston Marathon is a highly regarded event in the running world, not just for its prestige and challenging course, but also for its implementation of a psychology team to support runners. The 2013 Boston Marathon bombings underscored the essential role that mental health support plays at this event, prompting the development and expansion of its innovative care model. This review critically outlines, evaluates, and analyzes the approach and effectiveness of the psychological care model provided to runners on race day as part of the Boston Marathon medical team, including the standard of care, how it functions, and best practices for other marathons.

"They made me feel like I mattered": a qualitative study of how mobile crisis teams can support people experiencing homelessness.

Background: Mobile crisis teams (MCTs) can be important alternatives to emergency medical services or law enforcement for low-acuity 911 calls. MCTs address crises by de-escalating non-violent situations related to mental health or substance use disorders and concurrent social needs, which are common among people experiencing homelessness (PEH). We sought to explore how an MCT in one city served the needs and supported the long- and short-term goals of PEH who had recently received MCT services.

Cognitive Behavioral Program for the Prevention of Depression in At-Risk Adolescents: Isolating the Effects of Dose.

The current study estimated effects of intervention dose (attendance) of a cognitive behavioral prevention (CBP) program on depression-free days (DFD) in adolescent offspring of parents with a history of depression. As part of secondary analyses of a multi-site randomized controlled trial, we analyzed the complete intention-to-treat sample of 316 at-risk adolescents ages 13-17. Youth were randomly assigned to the CBP program plus usual care (n=159) or to usual care alone (n=157).

RNA-Seq time-course analysis of neural precursor cell transcriptome in response to herpes simplex Virus-1 infection.

The neurogenic niches within the central nervous system serve as essential reservoirs for neural precursor cells (NPCs), playing a crucial role in neurogenesis. However, these NPCs are particularly vulnerable to infection by the herpes simplex virus 1 (HSV-1). In the present study, we investigated the changes in the transcriptome of NPCs in response to HSV-1 infection using bulk RNA-Seq, compared to those of uninfected samples, at different time points post infection and in the presence or absence of antivirals.

Longitudinal study of peer victimization, social support, and mental health during early adolescence.

Background: Peer victimization predicts the development of mental health symptoms in the transition to adolescence, but it is unclear whether and how parents and school environments can buffer this link.

Methods: We analyzed two-year longitudinal data from the Adolescent Brain Cognitive Development (ABCD) study, involving a diverse sample of 11 844 children across the United States (average at baseline = 9.91 years; standard deviation = 0.

A multicellular brain spheroid model for studying the mechanisms and bioeffects of ultrasound-enhanced drug penetration beyond the blood‒brain barrier.

The blood‒brain barrier (BBB) acts as a hindrance to drug therapy reaching the brain. With an increasing incidence of neurovascular diseases and brain cancer metastases, there is a need for an ideal in vitro model to develop novel methodologies for enhancing drug delivery to the brain. Here, we established a multicellular human brain spheroid model that mimics the BBB both architecturally and functionally.

State-level working memory and dysregulated eating in children and adolescents: An exploratory ecological momentary assessment study.

Background: Children with loss of control (LOC) eating and overweight/obesity have relative deficiencies in trait-level working memory (WM), which may limit adaptive responding to intra- and extra-personal cues related to eating. Understanding of how WM performance relates to eating behavior in real-time is currently limited.

Methods: We studied 32 youth (ages 10-17 years) with LOC eating and overweight/obesity (LOC-OW; n = 9), overweight/obesity only (OW; n = 16), and non-overweight status (NW; n = 7).

Early indicators of response to transdiagnostic treatment of pediatric anxiety and depression.

Background: Pediatric anxiety and depression are prevalent, impairing, and highly comorbid. Available evidence-based treatments have an average response rate of 60%. One path to increasing response may be to identify likely non-responders midway through treatment to adjust course prior to completing an episode of care.

Adapting family-based treatment for adolescent anorexia nervosa delivered in the home: A novel approach for improving access to care and generalizability of skill acquisition.

Background: Anorexia nervosa (AN) is a serious mental illness associated with high rates of morbidity and mortality. Family-based treatment (FBT) is a well-established treatment for adolescent AN, yet it is underutilized in community settings and is unavailable to many families, particularly those from lower income and racial and ethnic minority backgrounds. Furthermore, some families do not respond optimally to FBT, possibly because of challenges translating skills acquired in office-based treatment settings to naturalistic settings.

Nurse-led pre-test counseling for Alzheimer's disease biomarker testing: Knowledge and skills required to meet the needs of patients and families.

Introduction: Biomarker testing for Alzheimer's disease and related disorders (ADRD) brings new opportunities for nurses to foster shared decision-making by leading pre-test counseling (PTC) for patients and families.

Methods: Audio-recordings of 18 nurse-led PTC sessions were analyzed to characterize questions posed by patient and family members dyads considering whether to pursue amyloid positron emission tomography.

Results: Sessions lasted 20 to 75 minutes and generated rich discussion of the purpose and potential implications of amyloid imaging.

Enhanced efficacy of CBT following augmentation with amygdala rtfMRI neurofeedback in depression.

Background: Despite cognitive behavioral therapy (CBT) being a standard treatment in major depressive disorder (MDD), nearly half of patients do not respond. As one of the predictors of CBT's efficacy is amygdala reactivity to positive information, which is often decreased in MDD, we explored whether real-time fMRI neurofeedback (rtfMRI-nf) training to increase amygdala responses during positive memory recall prior CBT would enhance its efficacy.

Methods: In a double-blind, placebo controlled, randomized clinical trial, 35 adults with MDD received two sessions of rtfMRI-nf training to increase their amygdala (experimental group, n = 16) or parietal (control group, n = 19) responses during positive memory neurofeedback prior to receiving 10 CBT sessions.

Change in marijuana use from adolescence to young adulthood and its relation to gestational alcohol and marijuana exposure.

Introduction: Many studies have examined changes in marijuana use across adolescence, but few have examined factors associated with transitions from adolescence to young adulthood. We examined prenatal exposures to alcohol and marijuana and adolescent risk and protective factors that best distinguished among abstinence, continuity, or cessation of marijuana use from 16 to 22 years.

Method: Data were from the Maternal Health Practices and Child Development Project at the prenatal and 16- and 22-year follow-up phases.

Clinical Issues in the Assessment of Competency.

The evaluation of a patient's competency to consent to treatment, regardless of the test of competency used, can be substantially affected by a number of clinical factors. The authors point out that, in assessing competency, the clinician must consider 1) psychodynamic elements of the patient's personality, 2) the accuracy of the historical information conveyed by the patient, 3) the accuracy and completeness of the information disclosed to the patient, 4) the stability of the patient's mental status over time, and 5) the effect of the setting in which consent is obtained. Inattention to these factors can lead to errors in assessment of competency that can have important implications for patient care.

A mentored hands-on training model for scaling up implementation and intervention research in India: "connecting the dots".

Despite the high burden of mental disorders in low- and middle-income countries (LMICs), less than 25% of those in need have access to appropriate services, in part due to a scarcity of locally relevant, evidence-based interventions and models of care. To address this gap, researchers from India and the United States and the Indian Council of Medical Research (ICMR) collaboratively developed a "Grantathon" model to provide mentored research training to 24 new principal investigators (PIs). This included a week-long didactic training, a customized web-based data entry/analysis system and a National Coordination Unit (NCU) to support PIs and track process objectives.

Truncated ring-A amaryllidaceae alkaloid modulates the host cell integrated stress response, exhibiting antiviral activity to HSV-1 and SARSCoV-2.

The total synthesis of four novel mono-methoxy and hydroxyl substituted ring-A dihydronarciclasine derivatives enabled identification of the 7-hydroxyl derivative as a potent and selective antiviral agent targeting SARSCoV-2 and HSV-1. The concentration of this small molecule that inhibited HSV-1 infection by 50% (IC50), determined by using induced pluripotent stem cells (iPCS)-derived brain organ organoids generated from two iPCS lines, was estimated to be 0.504 µM and 0.

The Impaired Neurodevelopment of Human Neural Rosettes in HSV-1-Infected Early Brain Organoids.

Intrauterine infections during pregnancy by herpes simplex virus (HSV) can cause significant neurodevelopmental deficits in the unborn/newborn, but clinical studies of pathogenesis are challenging, and while animal models can model some aspects of disease, in vitro studies of human neural cells provide a critical platform for more mechanistic studies. We utilized a reductionist approach to model neurodevelopmental outcomes of HSV-1 infection of neural rosettes, which represent the in vitro equivalent of differentiating neural tubes. Specifically, we employed early-stage brain organoids (ES-organoids) composed of human induced pluripotent stem cells (hiPSCs)-derived neural rosettes to investigate aspects of the potential neuropathological effects induced by the HSV-1 infections on neurodevelopment.

iPSC-Derived Neurons from Patients with POLG Mutations Exhibit Decreased Mitochondrial Content and Dendrite Simplification.

Mutations in POLG, the gene encoding the catalytic subunit of DNA polymerase gamma, result in clinical syndromes characterized by mitochondrial DNA (mtDNA) depletion in affected tissues with variable organ involvement. The brain is one of the most affected organs, and symptoms include intractable seizures, developmental delay, dementia, and ataxia. Patient-derived induced pluripotent stem cells (iPSCs) provide opportunities to explore mechanisms in affected cell types and potential therapeutic strategies.

Pharmacologic Treatment of Sleep Disorders in Pregnancy.

Pregnancy is a unique physiologic state whose characteristics often predispose women to new-onset sleep disturbances or exacerbations of preexisting sleep disorders. Pregnancy-related factors that can disrupt sleep include heartburn, nocturnal oxytocin secretion, nocturia, and fetal movement. Sleep disorders in pregnancy include insomnia (primary and secondary), restless legs syndrome, and narcolepsy.

Behavioral and neuroimaging evidence prodromal to major depressive disorder onset in a young adult without personal or family history of psychiatric disorder: Case report.

Background: Subthreshold symptoms of major depressive disorder (MDD) may be underreported due to stigma and/or cognitive impairment associated with this illness. Identifying objective behavioral and neural markers prodromal to MDD onset would help overcome this bias. This case study reports prospective behavioral and neuroimaging evidence prodromal to MDD onset in a young adult without prior personal or family history of psychiatric disorders who was identified during a longitudinal study of mood disorders.

Herpesvirus Infections in the Human Brain: A Neural Cell Model of the Complement System Derived from Induced Pluripotent Stem Cells.

Background: Herpesviruses alter cognitive functions in humans following acute infections; progressive cognitive decline and dementia have also been suggested. It is important to understand the pathogenic mechanisms of such infections. The complement system - comprising functionally related proteins integral for systemic innate and adaptive immunity - is an important component of host responses.