Neuroimaging alterations and relapse in early-stage psychosis.

Background: Recent reports have indicated that symptom exacerbation after a period of improvement, referred to as relapse, in early-stage psychosis could result in brain changes and poor disease outcomes. We hypothesized that substantial neuroimaging alterations may exist among patients who experience relapse in early-stage psychosis.

Methods: We studied patients with psychosis within 2 years after the first psychotic event and healthy controls.

Brain regions associated with olfactory dysfunction in first episode psychosis patients.

Objectives: Olfactory dysfunction is reproducibly reported in psychotic disorders, particularly in association with negative symptoms. The superior frontal gyrus (SFG) has been frequently studied in patients with psychotic disorders, in particular with their associations with negative symptoms. The relationship between olfactory functions and brain structure has been studied in healthy controls (HCs).

Sex-specific involvement of the Notch-JAG pathway in social recognition.

Under the hypothesis that olfactory neural epithelium gene expression profiles may be useful to look for disease-relevant neuronal signatures, we examined microarray gene expression in olfactory neuronal cells and underscored Notch-JAG pathway molecules in association with schizophrenia (SZ). The microarray profiling study underscored JAG1 as the most promising candidate. Combined with further validation with real-time PCR, downregulation of NOTCH1 was statistically significant.

From population to neuron: exploring common mediators for metabolic problems and mental illnesses.

Major mental illnesses such as schizophrenia (SZ) and bipolar disorder (BP) frequently accompany metabolic conditions, but their relationship is still unclear, in particular at the mechanistic level. We implemented an approach of "from population to neuron", combining population-based epidemiological analysis with neurobiological experiments using cell and animal models based on a hypothesis built from the epidemiological study. We characterized high-quality population data, olfactory neuronal cells biopsied from patients with SZ or BP, and healthy subjects, as well as mice genetically modified for insulin signaling.

A multimodal approach to studying the relationship between peripheral glutathione, brain glutamate, and cognition in health and in schizophrenia.

Involvement of oxidative stress in the pathophysiology of schizophrenia (SZ) is suggested by studies of peripheral tissue. Nonetheless, it is unclear how such biological changes are linked to relevant, pathological neurochemistry, and brain function. We designed a multi-faceted study by combining biochemistry, neuroimaging, and neuropsychology to test how peripheral changes in a key marker for oxidative stress, glutathione (GSH), may associate with central neurochemicals or neuropsychological performance in health and in SZ.

Randomized controlled trial of a gluten-free diet in patients with schizophrenia positive for antigliadin antibodies (AGA IgG): a pilot feasibility study.

Background: Approximately one-third of people with schizophrenia have elevated levels of anti-gliadin antibodies of the immunoglobulin G type (AGA IgG) — a higher rate than seen in healthy controls. We performed the first double-blind clinical trial of gluten-free versus gluten-containing diets in a subset of patients with schizophrenia who were positive for AGA IgG.

Methods: In this pilot feasibility study, 16 participants with schizophrenia or schizoaffective disorder who had elevated AGA IgG (≥ 20 U) but were negative for celiac disease were admitted to an inpatient unit for a 5-week trial.

Lithium-associated transcriptional regulation of CRMP1 in patient-derived olfactory neurons and symptom changes in bipolar disorder.

There is growing evidence that lithium used in the treatment of bipolar disorder (BD) affects molecular targets that are involved in neuronal growth, survival, and maturation, but it remains unclear if neuronal alterations in any of these molecules predict specific symptom changes in BD patients undergoing lithium monotherapy. The goals of this study were to (a) determine which molecular changes in the olfactory neurons of symptomatic patients receiving lithium are associated with antimanic or antidepressant response, and (b) uncover novel intraneuronal regulatory mechanisms of lithium therapy. Twenty-two treatment-naïve non-smoking patients, with symptomatic BD underwent nasal biopsies for collection of olfactory tissues, prior to their treatment and following a 6-week course of lithium monotherapy.

Decoupling of Brain Temperature and Glutamate in Recent Onset of Schizophrenia: A 7T Proton Magnetic Resonance Spectroscopy Study.

Background: Converging evidence suggests that cerebral metabolic and cellular homeostasis is altered in patients with recent onset of schizophrenia. As a possible marker of metabolic changes that might link to altered neurotransmission, we used proton magnetic resonance spectroscopy to estimate brain temperature, and we evaluated its relationship to a relevant metabolite, glutamate, within this study population.

Methods: Using proton magnetic resonance spectroscopy at 7T, 20 patients with recent onset (≤24 months after first psychotic symptoms) of schizophrenia and 20 healthy control subjects were studied.

Approaches to neuromodulation for schizophrenia.

Based on the success of deep brain stimulation (DBS) for treating movement disorders, there is growing interest in using DBS to treat schizophrenia (SZ). We review the unmet needs of patients with SZ and the scientific rationale behind the DBS targets proposed in the literature in order to guide future development of DBS to treat this vulnerable patient population. SZ remains a devastating disorder despite treatment.

The Olfactory Neural Epithelium As a Tool in Neuroscience.

Capturing both dynamic changes (state) and persistent signatures (trait) directly associated with disease at the molecular level is crucial in modern medicine. The olfactory neural epithelium, easily accessible in clinical settings, is a promising surrogate model in translational brain medicine, complementing the limitations in current engineered cell models.

Hippocampal volume reduction correlates with apathy in traumatic brain injury, but not schizophrenia.

Apathy commonly accompanies both traumatic brain injury (TBI) and deficit syndrome schizophrenia (DSZ), despite unclear neurological bases. The authors examined differences in cortical thickness and subcortical/cerebellar regional volumes between adult TBI survivors, patients with DSZ, and healthy-control subjects by use of 3-D magnetic resonance imaging (MRI), and correlated imaging findings with clinical ratings of apathy and selected cognitive test scores. Imaging findings revealed specific areas of volume reduction in TBI survivors and areas of cortical thinning among patients with DSZ.

Olfactory cells via nasal biopsy reflect the developing brain in gene expression profiles: utility and limitation of the surrogate tissues in research for brain disorders.

Human olfactory cells obtained by rapid nasal biopsy have been suggested to be a good surrogate system to address brain disease-associated molecular changes. Nonetheless, whether use of this experimental strategy is justified remains unclear. Here we compared expression profiles of olfactory cells systematically with those from the brain tissues and other cells.

Reduced anterior cingulate gray matter volume and thickness in subjects with deficit schizophrenia.

Background: Patients with deficit schizophrenia (D-SZ) differ from patients with the non-deficit form of schizophrenia (ND-SZ) in several aspects such as risk factors, neurobiological correlates, treatment response and clinical outcome. It has been debated if brain morphology could differentiate D-SZ from ND-SZ. Anterior cingulate gyrus (ACG) region regulates cognitive and emotional processing and past studies reported structural changes in this region in patients with SZ.

Relationships between serum leptin level and severity of positive symptoms in schizophrenia.

The adipocytokine leptin is a key mediator of energy homeostasis. Recent papers have suggested that leptin may also have roles in the brain however it is unclear whether leptin is connected to symptoms of mental disorders. In this study, we sought to clarify the relationships between serum leptin level and psychopathology in schizophrenia (SZ) patients.

Confirmatory factor analysis reveals a latent cognitive structure common to bipolar disorder, schizophrenia, and normal controls.

Objective: We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups.

Methods: We assessed 576 adults (340 community controls, 126 adults with bipolar disorder, and 110 adults with schizophrenia) using 15 measures derived from nine cognitive tests. Confirmatory factor analysis (CFA) was conducted to examine the fit of a hypothesized six-factor model.

Adolescent stress-induced epigenetic control of dopaminergic neurons via glucocorticoids.

Environmental stressors during childhood and adolescence influence postnatal brain maturation and human behavioral patterns in adulthood. Accordingly, excess stressors result in adult-onset neuropsychiatric disorders. We describe an underlying mechanism in which glucocorticoids link adolescent stressors to epigenetic controls in neurons.

Subcortical dopaminergic deficits in a DISC1 mutant model: a study in direct reference to human molecular brain imaging.

Imaging of the human brain has been an invaluable aid in understanding neuropsychopharmacology and, in particular, the role of dopamine in the striatum in mental illness. Here, we report a study in a genetic mouse model for major mental illness guided by results from human brain imaging: a systematic study using small animal positron emission tomography (PET), autoradiography, microdialysis and molecular biology in a putative dominant-negative mutant DISC1 transgenic model. This mouse model showed augmented binding of radioligands to the dopamine D2 receptor (D2R) in the striatum as well as neurochemical and behavioral changes to methamphetamine administration.

Diabetes is associated with lower global cognitive function in schizophrenia.

Background: Co-morbidity of schizophrenia (SZ) and metabolic problems such as diabetes mellitus (DM) has been suggested by many studies. Nonetheless, it is still debated whether DM affects cognitive dysfunction associated with SZ and how much treatment for DM is beneficial for cognitive functions in SZ. We addressed these questions by re-assessing the cognitive dataset from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study.

Increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients.

Gluten can cause extraintestinal manifestations with or without gastrointestinal symptoms and elevated antitissue transglutaminase 2 (tTG2) autoantibodies. Organ-specific gluten reaction involves immune response toward other transglutaminase (TG) isoforms including tTG3 (expressed in the skin, leading to dermatitis herpetiformis) and tTG6 (expressed in the brain, causing gluten ataxia). This analysis focuses on tTG6 antibodies, which have never been studied before in schizophrenia (SZ) and its relationships to tTG2 and to antigliadin antibodies.

Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity.

Celiac Disease (CD) is an immune-mediated disease dependent on gluten (a protein present in wheat, rye or barley) that occurs in about 1% of the population and is generally characterized by gastrointestinal complaints. More recently the understanding and knowledge of gluten sensitivity (GS), has emerged as an illness distinct from celiac disease with an estimated prevalence 6 times that of CD. Gluten sensitive people do not have villous atrophy or antibodies that are present in celiac disease, but rather they can test positive for antibodies to gliadin.