Atlas of Gray Matter Volume Differences Across Psychiatric Conditions: A Systematic Review With a Novel Meta-Analysis That Considers Co-Occurring Disorders.

Background: Regional gray matter volume (GMV) differences between individuals with mental disorders and comparison participants may be confounded by co-occurring disorders. To disentangle disorder-specific GMV correlates, we conducted a large-scale multidisorder meta-analysis using a novel approach that explicitly models co-occurring disorders.

Methods: We systematically reviewed voxel-based morphometry studies indexed in PubMed and Scopus up to January 2023 that compared adults with major mental disorders (anorexia nervosa, schizophrenia spectrum, anxiety, bipolar, major depressive, obsessive-compulsive, and posttraumatic stress disorders plus attention-deficit/hyperactivity, autism spectrum, and borderline personality disorders) with comparison participants.

Identifying digital biomarkers of illness activity and treatment response in bipolar disorder with a novel wearable device (TIMEBASE): protocol for a pragmatic observational clinical study.

Background: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions.

Aims: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder.

Method: We designed a longitudinal observational study including 84 individuals.

Protocol for extracting and isolating porcine bone-marrow-derived macrophages from ribs.

Due to anatomical and biological similarities with humans, pigs are increasingly used for inflammation- and immune-related studies in biomedical research, including the field of osteonecrosis and osteoimmunology. Here, we present a protocol for rib extraction, isolation of the bone marrow by centrifugation, and processing to obtain bone-marrow-derived macrophages (BMDMs). Then, we describe the procedures of in vitro experiments to evaluate the cell phenotype.

Blood Cell Count Ratios at Baseline are Associated with Initial Clinical Response to Clozapine in Treatment-Resistant, Clozapine-Naïve, Schizophrenia-Spectrum Disorder.

Background: Clozapine is the recommended treatment for managing treatment-resistant schizophrenia (TRS), and immunological mechanisms may be involved in its unique antipsychotic efficacy. This study investigated whether baseline immune abnormalities measured with blood cell count ratios can predict the clinical response after initiating treatment with clozapine in patients with clozapine naïve TRS.

Methods: A longitudinal design was developed, involving 32 patients diagnosed with treatment-resistant, clozapine-naïve schizophrenia-spectrum disorder.

Inflammatory blood cells and ratios at remission for psychosis relapse prediction: A three-year follow-up of a cohort of first episodes of schizophrenia.

Background: The clinical course following a first episode of schizophrenia (FES) is often characterized by recurrent relapses, resulting in unfavorable clinical and functional outcomes. Inflammatory dysregulation has been implicated in relapse risk; however, the predictive value of inflammatory blood cells in clinically remitted patients after a FES has not been previously explored.

Methods: In this study, we closely monitored 111 patients in remission after a FES until relapse or a three-year follow-up endpoint.

Effects of the PAM of mGluR2, JNJ-46356479, on brain apoptotic protein levels in a mouse model of schizophrenia.

Current treatment for schizophrenia (SZ) ameliorates the positive symptoms, but is inefficient in treating the negative and cognitive symptoms. The SZ glutamatergic dysfunction hypothesis has opened new avenues in the development of novel drugs targeting the glutamate storm, an inducer of progressive neuropathological changes. Positive allosteric modulators of metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), reduce the presynaptic release of glutamate, which has previously been demonstrated to attenuate glutamate- and dopamine-induced apoptosis in human neuroblastoma cell cultures.

Exploring Digital Biomarkers of Illness Activity in Mood Episodes: Hypotheses Generating and Model Development Study.

Background: Depressive and manic episodes within bipolar disorder (BD) and major depressive disorder (MDD) involve altered mood, sleep, and activity, alongside physiological alterations wearables can capture.

Objective: Firstly, we explored whether physiological wearable data could predict (aim 1) the severity of an acute affective episode at the intra-individual level and (aim 2) the polarity of an acute affective episode and euthymia among different individuals. Secondarily, we explored which physiological data were related to prior predictions, generalization across patients, and associations between affective symptoms and physiological data.

Neurotoxic/Neuroprotective Effects of Clozapine and the Positive Allosteric Modulator of mGluR2 JNJ-46356479 in Human Neuroblastoma Cell Cultures.

Current antipsychotics (APs) effectively control positive psychotic symptoms, mainly by blocking dopamine (DA) D2 receptors, but have little effect on negative and cognitive symptoms. Increased glutamate (GLU) release would trigger neurotoxicity, leading to apoptosis and synaptic pruning, which is involved in the pathophysiology of schizophrenia. New pharmacological strategies are being developed such as positive allosteric modulators (PAMs) of the metabotropic GLU receptor 2 (mGluR2) that inhibit the presynaptic release of GLU.

The Effect of Clozapine and Novel Glutamate Modulator JNJ-46356479 on Nitrosative Stress in a Postnatal Murine Ketamine Model of Schizophrenia.

Schizophrenia (SZ) is a heterogeneous mental disorder, affecting ~1% of the worldwide population. One of the main pathophysiological theories of SZ is the imbalance of excitatory glutamatergic pyramidal neurons and inhibitory GABAergic interneurons, involving N-methyl-D-aspartate receptors (NMDAr). This may lead to local glutamate storms coupled with excessive dendritic pruning and subsequent cellular stress, including nitrosative stress, during a critical period of neurodevelopment, such as adolescence.

Early treatment with JNJ-46356479, a mGluR2 modulator, improves behavioral and neuropathological deficits in a postnatal ketamine mouse model of schizophrenia.

Positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), may mitigate the glutamate storm during the early stages of schizophrenia (SZ), which could be especially useful in the treatment of cognitive and negative symptoms. We evaluated the efficacy of early treatment with JNJ or clozapine (CLZ) in reversing behavioral and neuropathological deficits induced in a postnatal ketamine (KET) mouse model of SZ. Mice exposed to KET (30 mg/kg) on postnatal days (PND) 7, 9, and 11 received JNJ or CLZ (10 mg/kg) daily in the adolescent period (PND 35-60).

Removing the effects of the site in brain imaging machine-learning - Measurement and extendable benchmark.

Multisite machine-learning neuroimaging studies, such as those conducted by the ENIGMA Consortium, need to remove the differences between sites to avoid effects of the site (EoS) that may prevent or fraudulently help the creation of prediction models, leading to impoverished or inflated prediction accuracy. Unfortunately, we have shown earlier that current Methods Aiming to Remove the EoS (MAREoS, e.g.

Systematic Review of the Therapeutic Role of Apoptotic Inhibitors in Neurodegeneration and Their Potential Use in Schizophrenia.

Schizophrenia (SZ) is a deleterious brain disorder affecting cognition, emotion and reality perception. The most widely accepted neurochemical-hypothesis is the imbalance of neurotransmitter-systems. Depleted GABAergic-inhibitory function might produce a regionally-located dopaminergic and glutamatergic-storm in the brain.

The use of two Comfort Young Child Formulas in the dietary management of toddlers with functional constipation: a randomized controlled trial.

Background: Pharmacological intervention with laxatives is the conventional treatment for functional constipation (FC). Data to support the dietary management of FC is lacking. This study compared the efficacy of two Comfort young child formulas (YCFs) with regards to the maintenance of healthy stooling parameters in toddlers with a history of constipation.

Surgical wounding enhances pro-tumor macrophage responses and accelerates tumor growth and lung metastasis in a triple negative breast cancer mouse model.

Approximately one-third of all breast cancer mortality results from metastatic recurrence after initial success of surgery and/or therapy. Although primary tumor removal is widely accepted as beneficial, it has long been suspected that surgery itself contributes to accelerated metastatic recurrence. We investigated surgical wounding's impact on tumor progression and lung metastasis in a murine model of triple negative breast cancer (TNBC).

Sub-chronic oral toxicity screening of quercetin in mice.

Background: Quercetin is an organic flavonoid present in several fruits and vegetables. The anti-inflammatory, antiviral, antioxidant, cardio-protective, anti-carcinogenic and neuroprotective properties demonstrated by this dietary supplement endorses it as a possible treatment for inflammatory diseases and cancer. Unfortunately, conflicting research has cast uncertainties on the toxicity of quercetin.

5-Fluorouracil disrupts skeletal muscle immune cells and impairs skeletal muscle repair and remodeling.

5-Fluorouracil (5FU) remains a first-line chemotherapeutic for several cancers despite its established adverse side effects. Reduced blood counts with cytotoxic chemotherapies not only expose patients to infection and fatigue, but can disrupt tissue repair and remodeling, leading to lasting functional deficits. We sought to characterize the impact of 5FU-induced leukopenia on skeletal muscle in the context of remodeling.

Obesity reduced survival with 5-fluorouracil and did not protect against chemotherapy-induced cachexia or immune cell cytotoxicity in mice.

Fluorouracil/5-flourouracil (5FU) is a first-line chemotherapy drug for many cancer types; however, its associated toxicities contribute to poor quality of life and reduced dose intensities negatively impacting patient prognosis. While obesity remains a critical risk factor for most cancers, our understanding regarding how obesity may impact chemotherapy's toxicities is extremely limited. C56BL/6 mice were given high fat (Obese) or standard diets (Lean) for 4 months and then subjected to three cycles of 5FU (5d-40 mg/kg Lean Mass, 9d rest) or PBS vehicle control.

Shaped before birth: Obstetric complications identify a more severe clinical phenotype among patients presenting a first affective or non-affective episode of psychosis.

Obstetric complications (OCs) may contribute to the heterogeneity that characterizes psychiatric illness, particularly the phenotypic presentation of first episode psychoses (FEP). Our aim was to examine the relationship between OCs and socio-demographic, clinical, functioning and neuropsychological characteristics in affective and non-affective FEP. We performed a cross-sectional,study where we recruited participants with FEP between 2011 and 2021, and retrospectively assessed OCs using the Lewis-Murray scale.

Prodromal phase: Differences in prodromal symptoms, risk factors and markers of vulnerability in first episode mania versus first episode psychosis with onset in late adolescence or adulthood.

Objective: This study was aimed at identifying differences in the prodromal symptoms and their duration, risk factors and markers of vulnerability in patients presenting a first episode mania (FEM) or psychosis (FEP) with onset in late adolescence or adulthood in order to guide tailored treatment strategies.

Methods: Patients with a FEM or FEP underwent a clinical assessment. Prodromes were evaluated with the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R).

Focusing on Comorbidity-A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders.

Background: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information.

Objectives: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities.

Cariprazine-induced mania: A case series report.

Bipolar depression is the most prevalent phase of bipolar disorder (BD). There is a risk of inducing treatment-emergent affective switches (TEAS) with antidepressants (ADs). Hence, clinical guidelines do not recommend their use in monotherapy.

Perampanel-Induced Psychosis in a Young Woman: A Case Report.

Objectives: A case of perampanel-induced psychosis in a young woman is reported, a side effect that has only rarely been reported in the literature.

Methods: We describe a case of a young woman with epilepsy and no psychiatric history with perampanel-associated altered behavior and psychotic symptoms, requiring hospitalization in an acute psychiatry ward. We also provide a literature review on the possible neurobiological pathways implicated.