Exploring the relationship between melanopsin gene variants, sleep, and markers of brain health.

Introduction: Melanopsin is a photopigment with roles in mediating sleep and circadian-related processes, which are often disrupted in Alzheimer's disease (AD). Melanopsin also impacts cognition and synaptogenesis. This study investigated the associations between melanopsin genetic variants, sleep, and markers of brain health.

Speech, Language and Non-verbal Communication in CLN2 and CLN3 Batten Disease.

CLN2 and CLN3 diseases, the most common types of Batten disease (also known as neuronal ceroid lipofuscinosis), are childhood dementias associated with progressive loss of speech, language and feeding skills. Here we delineate speech, language, non-verbal communication and feeding phenotypes in 33 individuals (19 females) with a median age of 9.5 years (range 3-28 years); 16 had CLN2 and 17 CLN3 disease; 8/15 (53%) participants with CLN2 and 8/17 (47%) participants with CLN3 disease had speech and language impairments prior to genetic diagnosis.

Drug delivery strategies for the treatment of relapse behavior in substance use disorder- A systematic review.

Substance use disorders (SUDs) pose a significant global health challenge, with relapse being a major obstacle in achieving successful treatment outcomes. In recent years, drug delivery strategies have emerged as promising tools to improve treatment efficacy and patient compliance in the context of SUD. Here we explore a diverse range of drug delivery strategies that have been investigated for addressing relapse behavior in SUD.

The history of biomarkers in psychiatry: lessons learned, lessons forgotten, lessons rediscovered.

A quirky truth is that the oldest biomarker findings are largely metabolic. These had minimal impact on contemporary thought and research and were largely ignored. They have been rediscovered and validated almost 100 years later, informing our understanding of neurobiology and medical comorbidity and spurring contemporary treatment discovery efforts.

Unraveling the bidirectional link between cancer and dementia and the impact of cancer therapies on dementia risk: A systematic review and meta-analysis.

Observational studies on the cancer-dementia relationship have yielded controversial results. This study systematically reviews the evidence to clarify this association. We searched Embase, Global Health, Ovid Medline, and APA PsycInfo.

Finding the right dose: a scoping review examining facilitation as an implementation strategy for evidence-based stroke care.

Background: Despite evidence supporting interventions that improve outcomes for patients with stroke, their implementation remains suboptimal. Facilitation can support implementation of research into clinical practice by helping people develop the strategies to implement change. However, variability in the amount (dose) and type of facilitation activities/facilitator roles that make up the facilitation strategies (content), may affect the effectiveness of facilitation.

The associations between prenatal plastic phthalate exposure and lipid acylcarnitine levels in humans and mice.

Phthalates are ubiquitous environmental pollutants known for their endocrine-disrupting properties, particularly during critical periods such as pregnancy and early childhood. Phthalates alter lipid metabolism, but the role of prenatal exposure on the offspring lipidome is less understood. In particular, we focused on long chain acylcarnitines - intermediates of fatty acid oxidation that serve as potential biomarkers of mitochondrial function and energy metabolism.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

First out-of-bed mobilisation in adults with severe acquired brain injury in Scandinavian neurointensive care units: A survey of current clinical practice (FOOBScan).

Background: The harm-benefit balance for early out-of-bed mobilisation of patients with severe acquired brain injury (ABI) in neurointensive care units (neuro-ICUs) is unclear, and there are no clinical guidelines. This study aimed to survey the current clinical practice and perceptions among clinicians involved in first out-of-bed mobilisation in Scandinavian neuro-ICUs.

Methods: This was a cross-sectional, anonymous, web-based survey; the reporting follows the recommended CROSS checklist.

Trajectory of Depressive Symptoms in a Longitudinal Stroke Cohort.

Objectives: Knowledge of the trajectory of post-stroke depression is important to identify high-risk patients, develop precise management programs and enhance prognosis. We aimed to characterise the course of depressive symptoms within the first year post-stroke and to evaluate associations with time.

Materials And Methods: Depressive symptoms were measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) within the first week, and at 3- and 12-months post-stroke.

Development and Validation of a Tool to Predict Onset of Mild Cognitive Impairment and Alzheimer Dementia.

Importance: The ability to predict the onset of mild cognitive impairment (MCI) and Alzheimer dementia (AD) could allow older adults and clinicians to make informed decisions about dementia care.

Objective: To assess whether the age at onset of MCI and AD can be predicted using a statistical modeling approach.

Design, Setting, And Participants: This prognostic study used data from 2 aging and dementia cohort studies-the Australian Imaging, Biomarker and Lifestyle (AIBL) study and the Alzheimer's Disease Neuroimaging Initiative (ADNI)-for model development and validation of the Florey Dementia Index (FDI), a tool used to predict the age at onset of MCI and AD in older adults.

COCHLEA: Longitudinal Cognitive Performance of Older Adults with Hearing Loss and Cochlear Implants at 4.5-Year Follow-Up.

Objectives: Hearing loss is highly prevalent in older adults and is independently associated with accelerated cognitive decline. Cochlear implants are usually the only effective treatment for people with severe-profound hearing loss, who have the highest risk of cognitive decline and dementia, however, very few receive them. Current evidence of the effects of cochlear implant use on cognitive decline/dementia outcomes is limited and unclear.

Effect of ketamine on anxiety: findings from the Ketamine for Adult Depression Study.

Background: Anxiety disorders and treatment-resistant major depressive disorder (TRD) are often comorbid. Studies suggest ketamine has anxiolytic and antidepressant properties.

Aims: To investigate if subcutaneous racemic ketamine, delivered twice weekly for 4 weeks, reduces anxiety in people with TRD.

Clinical Pharmacology and Approach to Dose Selection of Emestedastat, a Novel Tissue Cortisol Synthesis Inhibitor for the Treatment of Central Nervous System Disease.

This review demonstrates the value of central pharmacodynamics (PD), including positron emission tomography (PET) and computerized cognitive testing, to supplement pharmacokinetic (PK) and peripheral PD for determining the target dose range for clinical efficacy testing of emestedastat, an 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) inhibitor. Combined data from 6 clinical trials in cognitively normal volunteers and patients with Alzheimer disease included a population PK model, endocrine PD, a human PET trial (11β-HSD1 brain imaging), and computerized cognitive testing. PK and PET findings were similar in volunteers and patients with Alzheimer disease.

In defence of ferroptosis.

Rampant phospholipid peroxidation initiated by iron causes ferroptosis unless this is restrained by cellular defences. Ferroptosis is increasingly implicated in a host of diseases, and unlike other cell death programs the physiological initiation of ferroptosis is conceived to occur not by an endogenous executioner, but by the withdrawal of cellular guardians that otherwise constantly oppose ferroptosis induction. Here, we profile key ferroptotic defence strategies including iron regulation, phospholipid modulation and enzymes and metabolite systems: glutathione reductase (GR), Ferroptosis suppressor protein 1 (FSP1), NAD(P)H Quinone Dehydrogenase 1 (NQO1), Dihydrofolate reductase (DHFR), retinal reductases and retinal dehydrogenases (RDH) and thioredoxin reductases (TR).

Sex-Based Differences in Endovascular Thrombectomy Outcomes for Large Ischemic Stroke: A SELECT2 Subanalysis.

Background: Several social and biological factors are shown to differentially affect stroke outcomes between men and women. We evaluated whether clinical outcomes and endovascular thrombectomy (EVT) treatment effects differed between the sexes in patients presenting with large ischemic stroke.

Methods: The SELECT2 trial (A Randomized Controlled Trial to Optimize Patient's Selection for Endovascular Treatment in Acute Ischemic Stroke) was a randomized controlled trial assessing the efficacy and safety of EVT in patients with large strokes across the United States, Canada, Europe, Australia, and New Zealand between October 2019 and September 2022.

The association between cytokines and cognitive function in patients with major depressive disorder and controls.

Background: Cognitive dysfunction is a symptom of depression (MDD). While the involvement of the immune system has long been suggested to contribute to the biological underpinnings of depression, less is known about the underpinnings of cognitive dysfunction. A recent genome-wide association study pointed to genes related to immune function to be relevant for cognitive processes in depression.

Magnetic Resonance Imaging of Gastric Motility in Conscious Rats.

Introduction: Gastrointestinal (GI) magnetic resonance imaging (MRI) enables simultaneous assessment of gastric peristalsis, emptying, and intestinal filling and transit. However, GI MRI in animals typically requires anesthesia, which complicates physiology and confounds interpretation and translation to humans. This study aimed to establish GI MRI in conscious rats, and for the first time, characterize GI motor functions in awake versus anesthetized conditions.

Developmental dysfunction in a preclinical model of Kcnq2 developmental and epileptic encephalopathy.

Background: Developmental and epileptic encephalopathies (DEE) are rare but severe neurodevelopmental disorders characterised by early-onset seizures often combined with developmental delay, behavioural and cognitive deficits. Treatment for DEEs is currently limited to seizure control and provides no benefits to the patients' developmental and cognitive outcomes. Genetic variants are the most common cause of DEE with KCNQ2 being one of the most frequently identified disease-causing genes.

A stratified treatment algorithm in psychiatry: a program on stratified pharmacogenomics in severe mental illness (Psych-STRATA): concept, objectives and methodologies of a multidisciplinary project funded by Horizon Europe.

Schizophrenia (SCZ), bipolar (BD) and major depression disorder (MDD) are severe psychiatric disorders that are challenging to treat, often leading to treatment resistance (TR). It is crucial to develop effective methods to identify and treat patients at risk of TR at an early stage in a personalized manner, considering their biological basis, their clinical and psychosocial characteristics. Effective translation of theoretical knowledge into clinical practice is essential for achieving this goal.

Lost and found: dynamics of relationship and employment status over time in people with affective and psychotic spectrum disorders.

Background: Employment and relationship are crucial for social integration. However, individuals with major psychiatric disorders often face challenges in these domains.

Aims: We investigated employment and relationship status changes among patients across the affective and psychotic spectrum - in comparison with healthy controls, examining whether diagnostic groups or functional levels influence these transitions.

The effect of ovariectomy, 17β-estradiol treatment, and progesterone treatment on dopaminergic regulation of prepulse inhibition in adult and adolescent female mice.

The aim of the present study was to investigate the role of ovarian hormones on dopaminergic regulation of prepulse inhibition (PPI), a measure of sensorimotor gating deficient in schizophrenia and other psychiatric illnesses. Either in adulthood (11 weeks of age) or adolescence (5 weeks of age), female mice underwent ovariectomy (OVX) and were implanted with 17β-estradiol, progesterone, or a combination of these hormones. All mice were tested in adulthood for the acute effect of the dopamine receptor agonist, apomorphine, on PPI.