Propylthiouracil-Induced Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis with Renal and Lung Involvement.

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is a rare and heterogeneous disease. Moreover, optimal treatment is still lacking. We described the case of a 44-year-old lady with underlying Graves' disease who had cough, blood-streaked sputum, and impaired renal function.

The Eph receptor A4 plays a role in demyelination and depression-related behavior.

Proper myelination of axons is crucial for normal sensory, motor, and cognitive function. Abnormal myelination is seen in brain disorders such as major depressive disorder (MDD), but the molecular mechanisms connecting demyelination with the pathobiology remain largely unknown. We observed demyelination and synaptic deficits in mice exposed to either chronic, unpredictable mild stress (CUMS) or LPS, 2 paradigms for inducing depression-like states.

One-Year Outcomes of Living Related Kidney Transplant in Patients With Preformed HLA Donor-Specific Antibodies: A Single-Center Experience in Malaysia.

The shortage of deceased donors led to an increase of living related renal transplant performed in the presence of donor-specific antibodies (DSAs) or ABO incompatibilities. There are various desensitization protocols that have been proposed. Here, we describe the outcome of these sensitized patients.

The glucocorticoid receptor-FKBP51 complex contributes to fear conditioning and posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) can develop after exposure to severe psychological trauma, leaving patients with disabling anxiety, nightmares, and flashbacks. Current treatments are only partially effective, and development of better treatments is hampered by limited knowledge of molecular mechanisms underlying PTSD. We have discovered that the glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP51) form a protein complex that is elevated in PTSD patients compared with unaffected control subjects, subjects exposed to trauma without PTSD, and patients with major depressive disorder (MDD).

Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice.

Psychosocial adversity in early life increases the likelihood of mental and physical illness, but the underlying mechanisms are poorly understood. Mgat5 is an N-acetylglucosaminyltransferase in the Golgi pathway that remodels the N-glycans of glycoproteins at the cell surface. Mice lacking Mgat5 display conditional phenotypes in behaviour, immunity, metabolism, aging and cancer susceptibility.

Neuronal calcium sensor-1 deletion in the mouse decreases motivation and dopamine release in the nucleus accumbens.

Calcium sensors detect intracellular calcium changes and interact with downstream targets to regulate many functions. Neuronal Calcium Sensor-1 (NCS-1) or Frequenin is widely expressed in the nervous system, and involved in neurotransmission, synaptic plasticity and learning. NCS-1 interacts with and regulates dopamine D2 receptor (D2R) internalization and is implicated in disorders like schizophrenia and substance abuse.

The Effects of Video Games on Cognition and Brain Structure: Potential Implications for Neuropsychiatric Disorders.

Video games are now a ubiquitous form of entertainment that has occasionally attracted negative attention. Video games have also been used to test cognitive function, as therapeutic interventions for neuropsychiatric disorders, and to explore mechanisms of experience-dependent structural brain changes. Here, we review current research on video games published from January 2011 to April 2014 with a focus on studies relating to mental health, cognition, and brain imaging.

Caution When Diagnosing Your Mouse With Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders.

Animal models are widely used in biomedical research, but their applicability to psychiatric disorders is less clear. There are several reasons for this, including 1) emergent features of psychiatric illness that are not captured by the sum of individual symptoms, 2) a lack of equivalency between model animal behavior and human psychiatric symptoms, and 3) the possibility that model organisms do not have (and may not be capable of having) the same illnesses as humans. Here, we discuss the effective use, and inherent limitations, of model animals for psychiatric research.

Blocking GluR2-GAPDH ameliorates experimental autoimmune encephalomyelitis.

Objective: Multiple sclerosis (MS) is the most common disabling neurological disease of young adults. The pathophysiological mechanism of MS remains largely unknown and no cure is available. Current clinical treatments for MS modulate the immune system, with the rationale that autoimmunity is at the core of MS pathophysiology.

Schizophrenia and Depression Co-Morbidity: What We have Learned from Animal Models.

Patients with schizophrenia are at an increased risk for the development of depression. Overlap in the symptoms and genetic risk factors between the two disorders suggests a common etiological mechanism may underlie the presentation of comorbid depression in schizophrenia. Understanding these shared mechanisms will be important in informing the development of new treatments.

A dopamine D2 receptor-DISC1 protein complex may contribute to antipsychotic-like effects.

Current antipsychotic drugs primarily target dopamine D2 receptors (D2Rs), in conjunction with other receptors such as those for serotonin. However, these drugs have serious side effects such as extrapyramidal symptoms (EPS) and diabetes. Identifying a specific D2R signaling pathway that could be targeted for antipsychotic effects, without inducing EPS, would be a significant improvement in the treatment of schizophrenia.

Ligand-gated ion channel interacting proteins and their role in neuroprotection.

Ion channel receptors are a vital component of nervous system signaling, allowing rapid and direct conversion of a chemical neurotransmitter message to an electrical current. In recent decades, it has become apparent that ionotropic receptors are regulated by protein-protein interactions with other ion channels, G-protein coupled receptors and intracellular proteins. These other proteins can also be modulated by these interactions with ion channel receptors.

Simulating real world functioning in schizophrenia using a naturalistic city environment and single-trial, goal-directed navigation.

Objective: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia and that would also complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogs.

Method: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience, and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks.

Maternal immune activation during gestation interacts with Disc1 point mutation to exacerbate schizophrenia-related behaviors in mice.

Schizophrenia is thought to result from interactions between susceptible genotypes and environmental risk factors. DISC1 is an important gene for schizophrenia and mood disorders based on both human and animal studies. In the present study we sought to investigate interactions between two distinct point mutations in the mouse Disc1 gene (L100P and Q31L) and maternal immune activation (MIA) during pregnancy with polyinosinic:polycytidylic acid (polyI:C).

Abnormal interneuron development in disrupted-in-schizophrenia-1 L100P mutant mice.

Background: Interneuron deficits are one of the most consistent findings in post-mortem studies of schizophrenia patients and are likely important in the cognitive deficits associated with schizophrenia. Disrupted-in-Schizophrenia 1 (DISC1), a strong susceptibility gene for schizophrenia and other mental illnesses, is involved in neurodevelopment, including that of interneurons. However, the mechanism by which DISC1 regulates interneuron development remains unknown.

Using rodents to model schizophrenia and substance use comorbidity.

Schizophrenia and substance use disorders (SUD) often occur together, yet it is unclear why this is the case or how best to manage dual diagnosis. Rodent models are well suited to study how genes and environment interact to impact neurodevelopment, brain function and behaviors relevant to dual diagnosis. Indeed a variety of rodent models for schizophrenia display behavioral and physiological features relevant to SUD including: neurodevelopmental models, models of a rare variant (Disc1), to models of common variants (neurexin, dysbindin and neuregulin), and models of various gene-drug interactions.

Prophylactic valproic acid treatment prevents schizophrenia-related behaviour in Disc1-L100P mutant mice.

Background: Schizophrenia is a neurodevelopmental disorder with onset early in adulthood. Disrupted-In-Schizophrenia-1 (DISC1) is a susceptibility gene for schizophrenia and other psychiatric disorders. Disc1-L100P mutant mice show behaviors relevant to schizophrenia at 12 weeks, but not at 8 weeks of age, and may be useful for investigating the onset of schizophrenia in early adulthood.

Disrupted-in-schizophrenia-1 Gln31Leu polymorphism results in social anhedonia associated with monoaminergic imbalance and reduction of CREB and β-arrestin-1,2 in the nucleus accumbens in a mouse model of depression.

Disrupted-in-schizophrenia-1 (DISC1) is associated with mental disorders, including major depression. We previously showed that DISC1-Q31L mutant mice have depression-like behaviors and can therefore be used to study neurobiological mechanisms of depression and antidepressant (AD) medication action. First, we found reduced levels of dopamine, serotonin and norepinephrine in the nucleus accumbens (NAC) of DISC1-Q31L mutants.

5-hmC in the brain is abundant in synaptic genes and shows differences at the exon-intron boundary.

The 5-methylcytosine (5-mC) derivative 5-hydroxymethylcytosine (5-hmC) is abundant in the brain for unknown reasons. Here we characterize the genomic distribution of 5-hmC and 5-mC in human and mouse tissues. We assayed 5-hmC by using glucosylation coupled with restriction-enzyme digestion and microarray analysis.

The role of cognitive biases and personality variables in subclinical delusional ideation.

Introduction: A number of cognitive biases, most notably a data gathering bias characterised by "jumping to conclusions" (JTC), and the "bias against disconfirmatory evidence" (BADE), have been shown to be associated with delusions and subclinical delusional ideation. Certain personality variables, particularly "openness to experience", are thought to be associated with schizotypy.

Methods: Using structural equation modelling, we examined the association between two higher order subfactors ("aspects") of "openness to experience" (labelled "openness" and "intellect"), these cognitive biases, and their relationship to subclinical delusional ideation in 121 healthy, nonpsychiatric controls.

Social defeat interacts with Disc1 mutations in the mouse to affect behavior.

DISC1 (Disrupted-in-schizophrenia 1) is a strong candidate susceptibility gene for psychiatric disease that was originally discovered in a family with a chromosomal translocation severing this gene. Although the family members with the translocation had an identical genetic mutation, their clinical diagnosis and presentation varied significantly. Gene-environment interactions have been proposed as a mechanism underlying the complex heritability and variable phenotype of psychiatric disorders such as major depressive disorder and schizophrenia.