Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders.

Importance: As an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.

Objective: To determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.

Investigation of choroid plexus variability in schizophrenia-spectrum disorders-insights from a multimodal study.

Previous studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions associated with peripheral inflammation in SSD.

Signature of Altered Retinal Microstructures and Electrophysiology in Schizophrenia Spectrum Disorders Is Associated With Disease Severity and Polygenic Risk.

Background: Optical coherence tomography and electroretinography studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSDs). However, it remains unclear which specific retinal layers are affected; how the retina, brain, and clinical symptomatology are connected; and how alterations of the visual system are related to genetic disease risk.

Methods: Optical coherence tomography, electroretinography, and brain magnetic resonance imaging were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSDs and 130 healthy control individuals.

Massively parallel functional dissection of schizophrenia-associated noncoding genetic variants.

Schizophrenia (SCZ) is a highly heritable mental disorder with thousands of associated genetic variants located mostly in the noncoding space of the genome. Translating these associations into insights regarding the underlying pathomechanisms has been challenging because the causal variants, their mechanisms of action, and their target genes remain largely unknown. We implemented a massively parallel variant annotation pipeline (MVAP) to perform SCZ variant-to-function mapping at scale in disease-relevant neural cell types.

The multimodal Munich Clinical Deep Phenotyping study to bridge the translational gap in severe mental illness treatment research.

Introduction: Treatment of severe mental illness (SMI) symptoms, especially negative symptoms and cognitive dysfunction in schizophrenia, remains a major unmet need. There is good evidence that SMIs have a strong genetic background and are characterized by multiple biological alterations, including disturbed brain circuits and connectivity, dysregulated neuronal excitation-inhibition, disturbed dopaminergic and glutamatergic pathways, and partially dysregulated inflammatory processes. The ways in which the dysregulated signaling pathways are interconnected remains largely unknown, in part because well-characterized clinical studies on comprehensive biomaterial are lacking.

Disturbed Oligodendroglial Maturation Causes Cognitive Dysfunction in Schizophrenia: A New Hypothesis.

Background And Hypothesis: Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia.

Blood-brain barrier dysfunction and folate and vitamin B12 levels in first-episode schizophrenia-spectrum psychosis: a retrospective chart review.

Vitamin deficiency syndromes and blood-brain barrier (BBB) dysfunction are frequent phenomena in psychiatric conditions. We analysed the largest available first-episode schizophrenia-spectrum psychosis (FEP) cohort to date regarding routine cerebrospinal fluid (CSF) and blood parameters to investigate the association between vitamin deficiencies (vitamin B12 and folate) and BBB impairments in FEP. We report a retrospective analysis of clinical data from all inpatients that were admitted to our tertiary care hospital with an ICD-10 diagnosis of a first-episode F2x (schizophrenia-spectrum) between January 1, 2008 and August 1, 2018 and underwent a lumbar puncture, blood-based vitamin status diagnostics and neuroimaging within the clinical routine.

Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study.

Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG).

Spironolactone alleviates schizophrenia-related reversal learning in Tcf4 transgenic mice subjected to social defeat.

Cognitive deficits are a hallmark of schizophrenia, for which no convincing pharmacological treatment option is currently available. Here, we tested spironolactone as a repurposed compound in Tcf4 transgenic mice subjected to psychosocial stress. In this '2-hit' gene by environment mouse (GxE) model, the animals showed schizophrenia-related cognitive deficits.

Biobanking in everyday clinical practice in psychiatry-The Munich Mental Health Biobank.

Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was established in 2019 to collect, store, connect, and supply such high-quality phenotypic data and biosamples from patients and study participants, including healthy controls, recruited at the Department of Psychiatry and Psychotherapy (DPP) and the Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany. Participants are asked to complete a questionnaire that assesses sociodemographic and cross-diagnostic clinical information, provide blood samples, and grant access to their existing medical records.

Optical coherence tomography reveals retinal thinning in schizophrenia spectrum disorders.

Background: Schizophrenia spectrum disorders (SSDs) are presumed to be associated with retinal thinning. However, evidence is lacking as to whether these retinal alterations reflect a disease-specific process or are rather a consequence of comorbid diseases or concomitant microvascular impairment.

Methods: The study included 126 eyes of 65 patients with SSDs and 143 eyes of 72 healthy controls.

Expression of Lineage Transcription Factors Identifies Differences in Transition States of Induced Human Oligodendrocyte Differentiation.

Oligodendrocytes (OLs) are critical for myelination and are implicated in several brain disorders. Directed differentiation of human-induced OLs (iOLs) from pluripotent stem cells can be achieved by forced expression of different combinations of the transcription factors SOX10 (S), OLIG2 (O), and NKX6.2 (N).

Cognitive and functional deficits are associated with white matter abnormalities in two independent cohorts of patients with schizophrenia.

Background: Significant evidence links white matter (WM) microstructural abnormalities to cognitive impairment in schizophrenia (SZ), but the relationship of these abnormalities with functional outcome remains unclear.

Methods: In two independent cohorts (C1, C2), patients with SZ were divided into two subgroups: patients with higher cognitive performance (SZ-HCP-C1, n = 25; SZ-HCP-C2, n = 24) and patients with lower cognitive performance (SZ-LCP-C1, n = 25; SZ-LCP-C2, n = 24). Healthy controls (HC) were included in both cohorts (HC-C1, n = 52; HC-C2, n = 27).

Differential gene regulation in the anterior cingulate cortex and superior temporal cortex in schizophrenia: A molecular network approach.

The closely connected anterior cingulate cortex (ACC) and superior temporal cortex (STC) are important for higher cognitive functions. Both brain regions are disturbed in schizophrenia, i.e.

Role of psychiatric hospitals during a pandemic: introducing the Munich Psychiatric COVID-19 Pandemic Contingency Plan.

Background: Psychiatry is facing major challenges during the current coronavirus disease 2019 (COVID)-19 pandemic. These challenges involve its actual and perceived role within the medical system, in particular how psychiatric hospitals can maintain their core mission of attending to people with mental illness while at the same time providing relief to overstretched general medicine services. Although psychiatric disorders comprise the leading cause of the global burden of disease, mental healthcare has been deemphasised in the wake of the onslaught of the pandemic: to make room for emergency care, psychiatric wards have been downsized, clinics closed, psychiatric support systems discontinued and so on.

Classical blood biomarkers identify patients with higher risk for relapse 6 months after alcohol withdrawal treatment.

This naturalistic study among patients with alcohol dependence examined whether routine blood biomarkers could help to identify patients with high risk for relapse after withdrawal treatment. In a longitudinal study with 6-month follow-up among 133 patients with alcohol dependence who received inpatient alcohol withdrawal treatment, we investigated the usefulness of routine blood biomarkers and clinical and sociodemographic factors for potential outcome prediction and risk stratification. Baseline routine blood biomarkers (gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT/GPT], aspartate aminotransferase [AST/GOT], mean cell volume of erythrocytes [MCV]), and clinical and sociodemographic characteristics were recorded at admission.

Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction.

Imaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity.

Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients.

Hippocampal volume decrease is a structural hallmark of schizophrenia (SCZ), and convergent evidence from postmortem and imaging studies suggests that it may be explained by changes in the cytoarchitecture of the cornu ammonis 4 (CA4) and dentate gyrus (DG) subfields. Increasing evidence indicates that aerobic exercise increases hippocampal volume in CA subfields and improves cognition in SCZ patients. Previous studies showed that the effects of exercise on the hippocampus might be connected to the polygenic burden of SCZ risk variants.

Association between altered hippocampal oligodendrocyte number and neuronal circuit structures in schizophrenia: a postmortem analysis.

In schizophrenia, decreased hippocampal volume, reduced oligodendrocyte numbers in hippocampal cornu ammonis (CA) subregions and reduced neuron number in the dentate gyrus have been reported; reduced oligodendrocyte numbers were significantly related to cognitive deficits. The hippocampus is involved in cognitive functions and connected to the hypothalamus, anterior thalamus, and cingulate cortex, forming the Papez circuit, and to the mediodorsal thalamus. The relationship between the volume of these interconnected regions and oligodendrocyte and neuron numbers in schizophrenia is unknown.

Studying and modulating schizophrenia-associated dysfunctions of oligodendrocytes with patient-specific cell systems.

Postmortem studies in patients with schizophrenia (SCZ) have revealed deficits in myelination, abnormalities in myelin gene expression and altered numbers of oligodendrocytes in the brain. However, gaining mechanistic insight into oligodendrocyte (OL) dysfunction and its contribution to SCZ has been challenging because of technical hurdles. The advent of individual patient-derived human-induced pluripotent stem cells (hiPSCs), combined with the generation of in principle any neuronal and glial cell type, including OLs and oligodendrocyte precursor cells (OPCs), holds great potential for understanding the molecular basis of the aetiopathogenesis of genetically complex psychiatric diseases such as SCZ and could pave the way towards personalized medicine.

Concomitant drug abuse of opioid dependent patients in maintenance treatment detected with a multi-target screening of oral fluid.

Background And Objectives: Numbers of drug-related deaths have been growing in Europe and the USA, especially those attributable to mixed drug consumption. Overdose deaths account for about one third up to one half of all illicit drug deaths worldwide. In most cases opioids are involved.

Correlation between weather and incidence of selected ophthalmological diagnoses: a database analysis.

Purpose: Our aim was to correlate the overall patient volume and the incidence of several ophthalmological diseases in our emergency department with weather data.

Patients And Methods: For data analysis, we used our clinical data warehouse and weather data. We investigated the weekly overall patient volume and the average weekly incidence of all encoded diagnoses of "conjunctivitis", "foreign body", "acute iridocyclitis", and "corneal abrasion".