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I am excited to share the preprint for my manuscript on interneuron proportion changes in Schizophrenia 🧠 🧬 We analyzed over 1300 post-mortem brain samples from the dorsolateral prefrontal cortex and subgenual anterior cingulate cortex, making use of diverse datatypes (bulk RNAseq, snRNAseq, FISH, LCMseq) to ascertain how GABAergic interneuron subtypes are affected in human schizophrenia (SCZ). Our main takeaways are as follows: 1️⃣ Interneuron subtypes (particularly SST and PVALB cells) are associated either negatively or positively with SCZ in an age-dependant manner. 2️⃣ Interneuron pathology appears to be linked to the age of SCZ onset, and potentially other proxies of SCZ symptom severity. 3️⃣ We see an unexpected preservation/relative increase of interneuron subtype proportions in older individuals with SCZ, suggesting potential resiliency mechanisms worth further exploration. A special thanks goes out to my supervisor, Shreejoy Tripathy, as well as co-authors Xiaolin (Cloris) Zhou, Keon Arbabi, Alex Gonzalez Segura, Nicole Endresz, Daniel Felsky, Andreea Diaconescu, and Etienne Sibille. Questions and comments are welcome - and stay tuned for other great work from our Computational Neurogenomics group at CAMH! 🎉 https://lnkd.in/ek_HcFkC

Introduction: Schizophrenia (SCZ) is a psychiatric disorder caused by environmental, social, and genetic factors. This phenomenon is a severe neuropsychiatric disorder with a 1% worldwide prevalence. As SCZ is an exclusively human disorder, animal models cannot mimic SCZ pathophysiology. Thus, it is crucial to develop a novel human-based specific model of SCZ to elucidate mechanisms of the occurrence of the disease. In this regard, reprogramming somatic cells to human-induced pluripotent stem cells (hiPSCs) serves as an expensive instrument for modeling SCZ.  Methods: In the present study, we directly reprogrammed the isolated human ear dermal fibroblasts (HDFs) from schizophrenic patients into hiPSCs using some episomal agents in Matrigel-coated plates. The existence of pluripotency markers was confirmed by the immunocytochemistry (ICC) test and alkaline phosphatase protocol. We performed karyotype analysis to ensure the maintenance of the normal chromosomes.  Results: Analysis of colonies exhibited intense alkaline phosphatase engagement and Oct4, SSEA4, Nanog, and Tra-1-60. HiPSCs showed normal karyotypes and were potent to differentiate into ectoderm, endoderm, and mesoderm.  Conclusion: Application of hiPSCs derived from schizophrenic patients would be a promising approach to treating SCZ. For checking the behavior of the cells during neurogenesis, we suggest further studies be applied. #Schizophrenia, #hiPSCs, #Fibroblast, #EpisomalVectors

Recent studies have highlighted sex-specific brain mechanisms in mice that influence resilience to chronic stress. Activation of somatostatin-positive neurons in the prelimbic cortex enhances stress resilience in male mice, while similar effects in female mice occur in the ventral hippocampus. These findings may shed light on the varying efficacy of antidepressants and guide future therapeutic developments. The research underscores the importance of considering sex differences in psychiatric disorder treatments, as gene expression changes linked to stress resilience differ significantly between male and female mice. This could inform personalized approaches in mental health treatment strategies.

As an engineer turned physician, I’m passionate about solving complex problems. Few challenges are as pressing or intricate as addressing mental health disorders. At atai Life Sciences, we take a pragmatic and innovative approach to drug development, focusing on creating treatments that are not just safe and effective, but also scalable and accessible. Even the most groundbreaking therapies can only change lives if they work in the real world. I recently joined Brandon Li on the Power to the Patient podcast to discuss: - How our approach aims to ensure treatments are both clinically effective and practical for clinics and patients - Why we focus on hard-to-treat conditions like treatment-resistant depression (TRD) and social anxiety disorder (SAD) - The importance of data and our upcoming Phase 2 data readouts in 2025 It’s a conversation about balancing bold ideas with real-world applicability to truly transform mental health care. Tune in to our full conversation below. Thank you, Brandon, for the thoughtful discussion!

Everything worth doing is probably hard right now… Excited to share my conversation with Srinivas Rao, Co-CEO of atai Life Sciences, where we explored the pragmatic strategies shaping the future of psychedelic therapies. We also delved into how atai is approaching drug development in areas with high unmet need like social anxiety disorder, TRD and cognitive impairment in schizophrenia. Srini's unique background in engineering and neuropharmacology offers a fascinating lens into how atai approaches drug development with pragmatism, and patient-centricity at its core. 🧠 Key highlights: - The evolution of atai Life Sciences, from a fund to a biotech company. - Innovative drug delivery approaches, like DMT oral thin films, and why simplicity and scalability matter. - Balancing diverse compounds and therapeutic areas with a focused portfolio strategy. - Advancing research in areas like social anxiety disorder and cognitive impairment in schizophrenia. - Tackling clinical trial challenges, including the placebo effect and trial design complexities. 🎧 Tune in to hear how Srini's pragmatic approach is redefining what’s possible in neuropsychiatric drug development. 👇 Links in comments #Neuropsychiatry #Psychedelics #DrugDevelopment #ClinicalResearch

🌟 Excited to share our latest research! 🌟 Ugne Simanaviciute investigated how maternal immune activation (MIA) affects neurodevelopment in rat offspring using high-speed videography to track whisker movements during object exploration. 🧠 Key Findings: - Female MIA-exposed rats showed attentional deficits. - Whisker tracking is a quick, non-invasive method for studying sensory and cognitive behaviours. This study also highlights the importance of considering sex differences in neurodevelopmental research. Check out the full paper for more details! #Neuroscience #Research #Neurodevelopment 📝 https://lnkd.in/e8mKz3Mp

For this week’s Friday Read, we focus on the recent study from David Shin in the lab of Tomasz J. Nowakowski University of California, San Francisco, which explores thalamic dysfunction in psychiatric disorders, focusing on the 22q11.2 microdeletion associated with increased risk. They used human pluripotent stem cell-derived organoids to investigate early thalamus development, revealing widespread transcriptional dysregulation and elevated FOXP2 expression in thalamic neurons and glia. From a co-culture model, they found that the microdeletion leads to thalamic axon overgrowth, mediated by FOXP2. These findings suggest dysregulated thalamic development contributes to schizophrenia-related neural phenotypes in 22q11.2 deletion syndrome, offering fascinating insights into the neuropsychiatric disorder's genetic mechanisms. It will be very interesting to see how human pluripotent stem cell-derived organoids continue to play a fundamental role in psychiatric disorders in the future! Read the full paper here: https://zurl.co/Uvfq #ScienceResearch #Organoids

The global rates of Alzheimer's and dementia, and therefore also of care cases, are rising rapidly, and although effective treatment methods that can delay the progression of the disease - such as Transcranial Pulse Stimulation (TPS) - are already available, they are not yet widespread enough.    This inevitably brings the importance of early detection and prevention more and more to the fore. New approaches in research such as innovative blood tests, time-saving brain scans and short language tests are intended to improve early detection, diagnosis and thus also the possibilities for preventive measures.   At the "32nd European Congress of Psychiatry" in Budapest, Hungary, researchers recently presented a 60-second language test that is designed to provide initial indications of possible dementia in this short period of time.   The test, developed by Dr. János Kálmán and his team at the University of Szeged in Hungary, is an automated procedure for speech analysis. The so-called Speech Gap Test (S-GAP test) is intended to make it easier for GPs in particular to refer patients to specialists more quickly in suspected cases. There are also plans to develop a more sophisticated version of the S-GAP test, which could combine temporal speech parameters with biomarkers or other clinical parameters.   A summary of the S-GAP test can be read on "Alzheimer Science":   https://lnkd.in/dvUtWTXc   #alzheimerscience #transcranialpulsestimulation #tps #alzheimers #alzheimersearlydetection #dementiaearlydetection #alzheimersprevention #dementiaprevention #speechgabtest #sgaptest #alzheimersearlydetection60seconds #janoskalman #universityszeged  

New Schizophrenia Assays for Screening Services 🧠💡 Exploring Schizophrenia Through Advanced In-Vitro Models 💡🧠 Schizophrenia, a complex disorder affecting 1% of the population, presents challenges in treatment, particularly in addressing negative symptoms and cognitive impairments. Traditional approaches have focused on managing positive symptoms, leaving significant therapeutic gaps. At NeuroProof, we're pioneering research in developing innovative in-vitro disease models to accelerate breakthroughs in schizophrenia drug discovery. 🔬 Our Approach Drawing on cutting-edge neuroscience, we focus on functional phenotypic in-vitro assays. These models leverage neuronal cell cultures on microelectrode arrays, challenged by disruptive agents like the Neisseria gonorrhoeae (NG) antibody. This novel approach mirrors critical neurodevelopmental processes implicated in schizophrenia, providing a platform to dissect disease mechanisms at a cellular level. Our electrophysiological assay corresponds with data from schizophrenic patients, offering insights into complex neural dynamics and promising new avenues for therapeutic intervention. 🌟 Advantages of Our Models Unlike traditional models, our assays offer a nuanced understanding of schizophrenia's complex neural dynamics. By analyzing electrical activity patterns using proprietary methodologies, we identify distinct phenotypic changes induced by our experimental perturbations. This enables targeted screening for compounds capable of reversing these aberrant patterns, potentially revolutionizing schizophrenia treatment strategies. 🔍 Innovative Insights Acknowledging schizophrenia's multifactorial origins—including genetic predispositions and neuroimmunological influences—we integrate developmental and immunological perspectives into our assays. This holistic approach mirrors recent findings implicating maternal immune activation and other environmental factors in disease onset. 🤝 Collaborate with Us Explore our comprehensive screening services tailored for schizophrenia and related disorders. From initial assay development to compound screening campaigns, NeuroProof offers integrated solutions to propel your research forward. Contact us to learn more about how our advanced models can accelerate your path to discovery. 🔑 Key Points to Highlight Focus on innovative in-vitro disease models for schizophrenia research. Utilization of neuronal cell cultures on microelectrode arrays with disruptive agents to test new generations of antipsychotics. Analysis of electrical activity patterns to identify phenotypic changes. Integration of developmental and neuroimmunological insights. Comprehensive screening services and collaborative opportunities are available. #SchizophreniaResearch #Neuroscience #InVitroModels #DrugDiscovery #SchizophreniaTreatment #NeuroProof

ARC-SV Unlocks Hidden Genomic Insights into Psychiatric Disorders 🧬🧠  A groundbreaking study in #Cell has leveraged ARC-SV (Accurate Reconstruction of Complex Structural Variants) to unravel the intricate role of complex structural variations (SVs) in human genomes, shedding new light on their connection to psychiatric disorders.  🔍 Key Findings:   - Using ARC-SV,a probabilistic and machine-learning-based method, researchers analyzed 19,652 genomes across diverse populations and 1,160 postmortem brain samples from donors with and without psychiatric disorders.   - They identified 50 million base pairs of complex SVs, many affecting regions critical to gene regulation and brain function.   - Brains of donors with psychiatric conditions like schizophrenia and bipolar disorder showed a 50% higher occurrence of disruptive SVs in key neuronal pathways.  🛠️ The Power of ARC-SV:   Traditional sequencing methods often miss these intricate genomic rearrangements. ARC-SV, a state-of-the-art computational tool, enables high-resolution detection and analysis of previously hidden SVs, providing unparalleled insight into their biological significance.  🌍 Why This Matters:   1️⃣ ARC-SV revealed population-specific SV patterns, emphasizing the importance of genomic diversity in global research.   2️⃣ It uncovered genetic disruptions in psychiatric disorders that could lead to targeted interventions.   3️⃣ By integrating advanced tools like ARC-SV, the study paves the way for precision medicine in mental health care.  📊 The Scale of Impact:   Psychiatric disorders affect over 280 million people worldwide, and this research marks a significant step toward addressing their underlying genetic complexities.  Follow Leon Zheng to join the unique journey of AI in 2025! #PrecisionMedicine#PsychiatricDisorders#MachineLearning Find the source of the image and full paper in the comment 👇