Schizophrenia

…and large-scale human genetics of schizophrenia. The postdoc leads projects on synaptic pruning and connections during adolescence using virus-based neural circuit mapping with molecular and pharmacological tools, works with computat

…in mental disorders, including schizophrenia and autism. However, the underlying mechanisms of pathology are unknown. I will present novel evidence on key organizational principles, structural, and molecular features of thalamocortical networks, as well as critical thalamic pathway interactions that are likely affected in disorders. This data can facilitate modeling typical and abnormal brain function

Hallucinations are percepts experienced in the absence of external sensory input. Patients with hallucinations show both behavioral and neural alterations in statistical learning in simple sensory tasks. Predictive processing accounts of hallucinations suggest that these alterations bias patients’ perception toward their sensory expectations. However, 1) whether this framework holds when considering real-world hallucinations with complex content and 2) which upstream neural mechanisms cause these alterations in learning are hotly debated. To address these questions, we used fMRI to record neur

Schizophrenia is a complex disorder known for its positive symptoms: delusions and hallucinations. However, the impact of schizophrenia on function is mostly due to its executive dysfunction. Mechanistically, it is known that the prefrontal cortex (PFC) is dysfunctional in this disorder and that there is a general excitatory/inhibitory (E/I) imbalance in the schizophrenia brain. However, whether schizophrenia executive dysfunction can be specifically attributed to prefrontal E/I imbalance is unknown. Here, through a series of experiments across schizophrenia-relevant mouse models, we show the

In schizophrenia, disrupted perceptual processes are attributed to both hallucinations and delusions in positive symptoms [1, 2]. However, it remains unclear how top-down and bottom-up processes are represented across a visual hierarchy related to distinct symptoms, such as hallucinations, delusions, and negative symptoms. Our goal is to identify the visual areas involved in aberrant top-down and bottom-up processes that contribute to distinct symptoms in schizophrenia. To investigate this, we conducted a functional magnetic resonance imaging (fMRI) experiment with a perceptual decision-making

Among the brain structures affected in Schizophrenia is the hippocampus. In addition to structural changes [1], dysfunctions of the synaptic plasticity have also been observed supporting cognitive impairment [2]. To study these phenomena in depth, we aim to develop and match two models of the pathology, computational and experimental. Our work is based on an existing computational hippocampus model [3] and a 3-hits mouse model [4]. For that purpose, we analyze electrophysiological signals recorded with Multi-Electrode Array (MEA) on hippocampal slices to extract synaptic transmission character

Schizophrenia is a debilitating psychiatric disorder presenting with delusions, hallucinations, and cognitive dysfunction, characterised by widespread aberrant connectivity both in early and chronic stages. One of the relatively most connected forebrain regions is the claustrum, which has been shown to have reduced volume in schizophrenia. However, whether claustrum microstructure and connectivity are altered remains unknown. We hypothesized aberrant claustrum structure and tract-based connectivity in individuals with recent-onset schizophrenia. Structural and diffusion-weighted MRI data from

Perineuronal nets (PNNs) are dense extracellular matrix around a subset of neurons, mostly parvalbumin neurons (PVNs), regulating plasticity. The sulfation pattern of chondroitin sulfate chains within PNNs is key to their functions. Chondroitin 4 sulfate (C4S) levels rise with brain maturation and then slowly toward late ageing. The shift toward increased C4S/C6S ratio observed at the end of critical period and ageing was proposed as the plasticity limiting factor and could potentially prevent aberrant plasticity. Knockout of chondroitin sulfotransferase 11 (Chst11), an enzyme for C4S sulfatio

Cognition is among the first domains to be affected in schizophrenia and can predict the onset of psychosis. Measuring cognitive changes in schizophrenia is a complex process, which often involves a battery of multiple tests, where individual performance is compared to the average performance of the healthy population. Animal models are often used to probe into mechanisms of cognitive dysfunction. However, animal models of cognitive dysfunction in schizophrenia and other disorders usually focus on a single cognitive domain using a limited number of cognitive assays. In addition, behavioral ana

Schizophrenia is a highly heterogeneous psychiatric disorder, which is elicited by multiple genetic and non-genetic factors. It remains insufficiently treatable with the current pharmaceutical approaches. In this study, we describe a new pathological mechanism and identify a new pharmacological treatment target with the use of a recently introduced ligand for it. An initial analysis of human gene polymorphisms and brain gene expression in schizophrenia patients identified an association of Smpd1 and Smpd3 genes coding for acid- (ASM) and neutral sphingomyelinase (NSM). In a rat model of amphet

…neuropsychiatric disorders such as schizophrenia, bipolar, and autism. However, the mechanism of action of the JNK pathway in the context of these diseases is unknown. We previously identified that inhibition of JNK in dentate gyrus granule cells of mouse hippocampus induces a low anxiety- and low depressive-like phenotype (Mohammad et al., Molecular Psychiatry, 2018). However, whether JNK pathway activity in other brain regions contributes to these behaviours is not known. Here we use cell restrictive exp

…a key component in the development of schizophrenia symptoms, with reduced PV protein levels found in cortical PV+ interneurons in individuals with schizophrenia. Rodent models of schizophrenia indicate that the medial prefrontal cortex (mPFC) is the main structure where PV neurons exhibit aberrant function. However, it is still

…of neuropsychiatric disorders, such as schizophrenia. Synaptic dysfunction in the prefrontal cortex, and its consequences on neuronal circuitry and behaviour, have been extensively linked to the disease. In this study, we are characterising the functional and behavioural consequences of a recently discovered, schizophrenia-associated variant in the CACNG2 gene, coding for the postsynaptic protein stargazin (StgSCZ). The aim of our study is to uncover how dysfunction at the level of the synapse in the prefrontal

…such as autism spectrum disorder, schizophrenia, and Phelan-McDermid syndrome. Since detailed knowledge of their effect on synaptic nanostructure remains limited, we investigated such alterations in ex11|SH3 SHANK3-KO mice combining expansion (ExM) and STED microscopy. This enabled high-resolution imaging of mosaic-like arrangements formed by synaptic proteins. We found distinct shape-profiles as fingerprints of the murine postsynaptic scaffold across brain regions and genotypes, as well as alterations in the spatial and molec

The molecular nature of psychiatric disorders such as schizophrenia and major depression is still unclear. Lipids may play an important role in the understanding of these disorders, as they are the most abundant yet poorly studied components of the human brain. In this work, we present a comparative lipidomic map of the human brain affected by schizophrenia or major depressive disorder. The study involved three groups of donors, 7 donors each, which included schizophrenic and depressive donors as well as healthy controls. The lipid composition of 36 brain regions was evaluated by liquid chroma

…disorders, such as psychosis, schizophrenia, bipolar disorder and depression. Previous studies have shown that mice lacking C3aR exhibit behavioural abnormalities, including anxiety, hyperactivity, and working memory deficit. These findings indicate that C3aR is involved in the development and/or function of brain circuits. We performed a brain imaging

Schizophrenia is a complex mental illness, with a higher risk of onset among young men. Schizophrenia is nowadays considered to result from a defective connectivity, having a neurodevelopmental origin, between several integrative regions. Morphological anomalies consistent with early brain development disturbances have been described at the level of the patients'left prefrontal cortex (PFC). Furthermore, psychotomimetic such as the noncompetitive NMDA/glutamate receptor antagonist ketamine, can induce psychotic symptoms in healthy subjects and exacerbate them in schizophrenia patients. Taking

…associated with heightened risks of schizophrenia and autism. Limited medication options coupled with social, cognitive, and adaptive challenges hinder the integration of affected individuals into society due to insufficient understanding of underlying pathophysiological mechanisms. To address this, we developed a triple transgenic mouse model combining the 15q13.3+/- microdeletion with TRAP2;Ai9,

Derived from the unique immune system of camelids, nanobodies are compact single-domainantibodies that have revolutionized the field of biomedical research. These miniaturized antibodies offer numerous advantages, including high specificity, stability, and ease of engineering. Interestingly, A2AR and mGlu5R form heteromers in the striatum, exhibiting synergistic transinhibition over striatal D2R signaling. 1 This oligomerization provides a unique pharmacological opportunity to explore whether the physical proximity of these receptors enables oligomer-dependent orthogonal targeting of counterpa

Schizophrenia, a complex neuropsychiatric condition impacting 0.5-1% of adults, manifests through positive, negative, and cognitive symptoms affecting emotions, thought processes, and perception. Onset typically occurs from late adolescence to early adulthood, with genetic and early-life environmental factors implicated in its strongly neurodevelopmental origin. The dopamine system plays a central role in schizophrenia's pathogenesis, with dopamine 2 receptor antagonists as the first line of treatment since the 1950s. Numerous studies highlight abnormal dopamine functions in schizophrenia pati

AbstractSchizophrenia is mental disorder characterized by a large variety of symptoms such as paranoia, delusions, lack of motivation and problems in attention and memory. In recent years it has been hypothesized that mitochondrial dysfunction and energy metabolism dysregulation may contribute to the pathophysiology of schizophrenia [1]. Therefore, we studied the mRNA expression of the prefrontal cortex (PFC) using the CommonMind data set [2] to find out if there is a significant enrichment of differentially expressed metabolism genes between control group and schizophrenia patients. In additi

…for neurodevelopmental disorders like schizophrenia and autism later in life.This study investigates the differential impact of MIA on neuronal progenitor cells at E10.5 (polyI:C administration at E9.5) by using single-cell RNA sequencing. Additionally, we examined the role of microglia in mediating the effects of MIA at different developmental stages.

Dopamine (DA) dysregulation has been linked to schizophrenia (SCZ) psychopathology for decades, but there is still an unmet need to identify underlying neural mechanisms. In particular, dopaminergic hyperactivity found in SCZ patients primarily in the associated/dorsomedial striatum (DMS), but not ventral striatum raises the necessity to address the role of the nigrostriatal pathways in SCZ. In order to study DA dysregulation relevant to human disease, we made use of the Df(16)A+/- mouse model of the 22q11.2 Deletion Syndrome, the most common chromosomal microdeletion and the highest genetic r

Background: Hippocampal memory deficit is an important symptom in patients with schizophrenia that responds poorly to antipsychotic treatment. Here, we investigated deficits in hippocampal long-term potentiation/depotentiation changes in the sub-chronic phencyclidine (scPCP) rat model for schizophrenia and how chronic exercise as a non-pharmacological treatment may produce hippocampal synaptic and cognitive improvements.Methods: 60 Female Lister Hooded rats (50 for acute recording and 10 for chronic recording) were dosed with either saline or PCP (2 mg/kg, i.p.) twice daily for seven days foll