New role of platelets in schizophrenia: predicting drug response.

Background: Elevated platelet count (PLTc) is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis. However, the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.

Aims: We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.

From cells to insights: the power of human pluripotent stem cell-derived cortical interneurons in psychiatric disorder modeling.

Psychiatric disorders, such as schizophrenia (SCZ) and autism spectrum disorders (ASD), represent a global health challenge with their poorly understood and complex etiologies. Cortical interneurons (cINs) are the primary inhibitory neurons in the cortex and their subtypes, especially those that are generated from the medial ganglionic emission (MGE) region, have been shown to play an important role in the pathogenesis of these psychiatric disorders. Recent advances in induced pluripotent stem cell (iPSC) technologies provide exciting opportunities to model and study these disorders using human iPSC-derived cINs.

Association of elevated levels of peripheral complement components with cortical thinning and impaired logical memory in drug-naïve patients with first-episode schizophrenia.

Schizophrenia has been linked to polymorphism in genes encoding components of the complement system, and hyperactive complement activity has been linked to immune dysfunction in schizophrenia patients. Whether and how specific complement components influence brain structure and cognition in the disease is unclear. Here we compared 52 drug-naïve patients with first-episode schizophrenia and 52 healthy controls in terms of levels of peripheral complement factors, cortical thickness (CT), logical memory and psychotic symptoms.

Frontostriatal circuitry and the tryptophan kynurenine pathway in major psychiatric disorders.

Rationale: An imbalance of the tryptophan kynurenine pathway (KP) commonly occurs in psychiatric disorders, though the neurocognitive and network-level effects of this aberration are unclear.

Objectives: In this study, we examined the connection between dysfunction in the frontostriatal brain circuits, imbalances in the tryptophan kynurenine pathway (KP), and neurocognition in major psychiatric disorders.

Methods: Forty first-episode medication-naive patients with schizophrenia (SCZ), fifty patients with bipolar disorder (BD), fifty patients with major depressive disorder (MDD), and forty-two healthy controls underwent resting-state functional magnetic resonance imaging.

Generation of Homogeneous Populations of Cortical Interneurons from Human Pluripotent Stem Cells.

Cortical interneurons (cINs), especially those that are derived from the medial ganglionic eminence (MGE) during early development, are associated with various neuropsychiatric disorders. Human pluripotent stem cell (hPSC)-derived cINs can provide unlimited cell sources for studying disease mechanisms and developing novel therapeutics. Here, we describe an optimized method to generate homogeneous cIN populations based on three-dimensional (3D) cIN sphere generation.

Decreased plasma neuropeptides in first-episode schizophrenia, bipolar disorder, major depressive disorder: associations with clinical symptoms and cognitive function.

Background: There is an urgent need to identify differentiating and disease-monitoring biomarkers of schizophrenia, bipolar disorders (BD), and major depressive disorders (MDD) to improve treatment and management.

Methods: We recruited 54 first-episode schizophrenia (FES) patients, 52 BD patients, 35 MDD patients, and 54 healthy controls from inpatient and outpatient clinics. -Melanocyte Stimulating Hormone (-MSH), -endorphin, neurotensin, orexin-A, oxytocin, and substance P were investigated using quantitative multiplex assay method.

YBX1-Mediated DNA Methylation-Dependent SHANK3 Expression in PBMCs and Developing Cortical Interneurons in Schizophrenia.

Schizophrenia (SCZ) is a severe psychiatric and neurodevelopmental disorder. The pathological process of SCZ starts early during development, way before the first onset of psychotic symptoms. DNA methylation plays an important role in regulating gene expression and dysregulated DNA methylation is involved in the pathogenesis of various diseases.

3,4-Dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide analogs act as potential AMPA receptor potentiators with antidepressant activity.

Major depressive disorder is a common psychiatric disorder, with ∼30% of patients suffering from treatment-resistant depression. Based on preclinical studies on ketamine, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) activation may be a promising therapeutic approach. In this study, we synthesized a series of novel 3,4-dihydrobenzo[e][1,2,3]oxathiazine 2,2-dioxide analogs and analyzed their potential as AMPAR potentiators.

Association of the plasma complement system with brain volume deficits in bipolar and major depressive disorders.

Background: Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders.

Methods: A total of 52 BD patients, 35 MDD patients, and 53 controls were recruited.

Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway.

Ketamine, a rapid-acting antidepressant drug, has been used to treat major depressive disorder and bipolar disorder (BD). Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in patients. Ketamine has also been applied to establish animal models of mania.

Mitochondrial dysfunction in psychiatric disorders.

Psychiatric disorders are a heterogeneous group of mental disorders with abnormal mental or behavioral patterns, which severely distress or disable affected individuals and can have a grave socioeconomic burden. Growing evidence indicates that mitochondrial function plays an important role in developing psychiatric disorders. This review discusses the neuropsychiatric consequences of mitochondrial abnormalities in both animal models and patients.

A combination of neuroimaging and plasma metabolomic analysis suggests inflammation is associated with white matter structural connectivity in major depressive disorder.

Background: Major depressive disorder (MDD) is a common mental disorder with unknown pathophysiology. The abnormality of white matter structural connectivity and dysregulation of metabolome in MDD had been widely reported previously. Exploration of the relationship between white matter structural connectivity and plasma metabolites would be helpful for explanation of molecular mechanism for the findings from neuroimaging researches in MDD.

Generation and characterization of human-derived iPSC lines from two cousins with schizophrenia and bipolar disorder and their unaffected cousin.

Schizophrenia (SCZ) and bipolar disorder (BD) are debilitating neurodevelopmental disorders with high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by three females. An adolescent female was clinically diagnosed as first-episode SCZ.

Correlation between reduced telomere length and behavioural and emotional problems in left-behind children in a rural area in China.

Evidence shows that being left behind experience (LBE) during childhood may increase the risks of poor psychopathological outcomes. However, it is unclear to what extent the mental health is affected by the LBE. Telomere length (TL), one of the most extensively studied biological markers of cellular ageing, provides a valuable tool for exploring the potential effects of parent-child separation on psychological problems by integrating genetic and environmental factors.

Generation and characterization of human-derived iPSC lines from one pair of dizygotic twins discordant for schizophrenia.

Schizophrenia (SCZ) is a debilitating neurodevelopmental disorder with a high heritability. In this study, peripheral blood mononuclear cells (PBMCs) were donated by a pair of dizygotic twins. The female was clinically diagnosed as SCZ by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria, and her unaffected male sibling was healthy control.

Alterations in CRY2 and PER3 gene expression associated with thalamic-limbic community structural abnormalities in patients with bipolar depression or unipolar depression.

Objectives The current study aimed to identify shared and distinct brain structure abnormalities and their relationships with the expression of circadian genes in patients with bipolar or unipolar depression. Method A total of 93 subjects participated in this study, including 32 patients with bipolar depression (BDP), 26 patients with unipolar depression (UDP) and 35 age- and sex-matched healthy controls. Brain structural magnetic resonance imaging scans were obtained, and optimized voxel-based morphometry was used to explore group differences in regional gray matter volume (GMV).

A plasma metabolomics study suggests alteration of multiple metabolic pathways in patients with bipolar disorder.

Previous omics studies have greatly contributed to our knowledge of bipolar disorder. Metabolomics is a relatively new field of omics science that can provide complementary insight into data obtained from genomics, transcriptomics or proteomics analyses. In this study, we aimed to identify metabolic pathways associated with bipolar disorder.

Migratory cortical interneuron-specific transcriptome abnormalities in schizophrenia.

Cortical interneurons (cINs) are substantially affected in Schizophrenia (SCZ) and enriched for SCZ heritability during development. To understand SCZ-specific changes in these cells during development, we isolated migratory cINs from cIN spheres derived from 5 healthy control (HC) and 5 SCZ induced pluripotent stem cell lines (iPSCs). Transcriptome analyses show dysregulation in extracellular matrix pathways as the major disturbances in SCZ migratory cINs, whereas sphere cINs show dysregulation in immune pathways.

Association Analysis Between Catechol-O-Methyltransferase Expression and Cognitive Function in Patients with Schizophrenia, Bipolar Disorder, or Major Depression.

Introduction: Schizophrenia, bipolar disorder (BD), and major depressive disorder are three common mental disorders. Although their diagnosis and treatment differ, they partially overlap.

Methods: To explore the similarities and characteristics of these three psychiatric diseases, an intelligence quotient (IQ) assessment was performed to evaluate cognitive deficits.

Valproate Reverses Mania-Like Behavior of Mouse and Alters Monoamine Neurotransmitters Metabolism in the Hippocampus.

Background: Mice with a deletion at exon 19 of the circadian locomotor output cycles Kaput gene ( ) exhibit mania-like behavior and have been one of the most common animal models for bipolar disorder (BD). The predictive validity of the was investigated via studies using lithium previously. Determination of effects of other mood stabilizers on mouse would be helpful for better understanding of the mechanism underlined.

Chronic lithium exposure attenuates ketamine-induced mania-like behavior and c-Fos expression in the forebrain of mice.

Ketamine, a dissociative anaesthetic, has been used in the treatment of major depressive disorder (MDD) as a rapid acting antidepressant drug. Recent studies have shown that ketamine may increase the potential risk of treatment-induced mania in MDD patients. Lithium is a well-known mood stabilizer and has been widely used for the treatment of mania.

Activated microglia cause metabolic disruptions in developmental cortical interneurons that persist in interneurons from individuals with schizophrenia.

The mechanisms by which prenatal immune activation increase the risk for neuropsychiatric disorders are unclear. Here, we generated developmental cortical interneurons (cINs)-which are known to be affected in schizophrenia (SCZ) when matured-from induced pluripotent stem cells (iPSCs) derived from healthy controls (HCs) and individuals with SCZ and co-cultured them with or without activated microglia. Co-culture with activated microglia disturbed metabolic pathways, as indicated by unbiased transcriptome analyses, and impaired mitochondrial function, arborization, synapse formation and synaptic GABA release.