Article
Biology
Paulina Barbara Lukow, Daniel Martins, Mattia Veronese, Anthony Christopher Vernon, Philip McGuire, Federico Edoardo Turkheimer, Gemma Modinos
Summary: Correlation studies between regional PET signal and gene expression levels of GABA receptors and inhibitory interneuron markers reveal insights into the molecular origin of GABA receptor PET tracer signal. This knowledge is crucial for understanding GABAergic neurotransmission and interpreting GABA receptor PET tracers in clinical populations.
COMMUNICATIONS BIOLOGY
(2022)
Article
Psychiatry
Brian Dean, Vahram Haroutunian, Elizabeth Scarr
Summary: This study found lower levels of cortical muscarinic M1 receptors (CHRM1) in older people with schizophrenia, and this loss of CHRM1 was associated with symptom severity. Compared to controls, people with schizophrenia showed lower levels of [3H]pirenzepine binding to CHRM1. A cut-off value of 121 fmol/mg protein for [3H]pirenzepine binding had a 90.7% specificity for diagnosing schizophrenia. Cognitive deficits were less severe in the muscarinic receptor deficit sub-group (MRDS) of schizophrenia, while the sub-group with normal radio-ligand binding had higher scores on the Clinical Dementia Rating Scale (CDR).
SCHIZOPHRENIA RESEARCH
(2023)
Article
Anesthesiology
Yukino Oshima, Makoto Sano, Ichie Kajiwara, Yoshimi Ichimaru, Tomoaki Itaya, Tomoya Kuramochi, Emiko Hayashi, Jinsuk Kim, Osamu Kitajima, Yohei Masugi, Atsushi Masamune, Hideaki Ijichi, Yukimoto Ishii, Takahiro Suzuki
Summary: In this study, we found that midazolam can inhibit the proliferation and inflammatory response of pancreatic ductal adenocarcinoma, thereby slowing down its progression. This drug also has analgesic effects on cancer-associated pain.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Neurosciences
Joshua M. Lorenz-Guertin, Nadya Povysheva, Caitlyn A. Chapman, Matthew L. Macdonald, Marco Fazzari, Aparna Nigam, Jessica L. Nuwer, Sabyasachi Das, Megan L. Brady, Katarina Vajn, Matthew J. Bambino, Susan T. Weintraub, Jon W. Johnson, Tija C. Jacob
Summary: Benzodiazepine drugs treat seizures, anxiety, insomnia, and alcohol withdrawal by enhancing GABA-A receptors containing γ2 subunits. However, their clinical use is hindered by tolerance and withdrawal symptoms. This study found that long-term treatment with benzodiazepines reduces sedative effects, alters GABA-A receptor distribution, decreases inhibitory tone, and increases glutamatergic neurotransmission.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Edison Leung, Ethan W. Lau, Andi Liang, Constanza de Dios, Robert Suchting, Linda Ostlundh, Joseph C. Masdeu, Masahiro Fujita, Marsal Sanches, Jair C. Soares, Sudhakar Selvaraj
Summary: This study systematically reviews the pathophysiological mechanisms of bipolar and major depressive disorders, focusing on synaptic proteins and RNA alterations. Meta-analysis results indicate specific changes in synaptic proteins and RNAs in both disorders, although conflicting results are observed due to small sample sizes and variations in data sources.
MOLECULAR PSYCHIATRY
(2022)
Article
Biochemistry & Molecular Biology
Ryoko Tanaka, Kosho Makino, Hidetsugu Tabata, Tetsuta Oshitari, Hideaki Natsugari, Hideyo Takahashi
Summary: Triazolobenzodiazepines with methyl substituents at C1 and C10 positions, as well as a chloro substituent at C2' of the pendant phenyl, were synthesized and their physicochemical properties and affinity at GABA(A) receptors were investigated. The results showed that the (a(1)R, a(2)S) isomers possessed higher activity than the (a(1)S, a(2)R) isomers. The absolute configurations of the compounds were determined based on CD spectra and comparison with reference compounds.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Review
Neurosciences
Brian Dean, Geor Bakker, Hiroki R. Ueda, Andrew B. Tobin, Alastair Brown, Richard A. A. Kanaan
Summary: Pre-clinical models, postmortem and neuroimaging studies all suggest that muscarinic receptors are involved in the molecular pathology of schizophrenia. Clinical trials have shown that activating central muscarinic M1 and M4 receptors can reduce the severity of symptoms. This review discusses the growing evidence for the critical roles of muscarinic M1 and M4 receptors in CNS functions and their implication in schizophrenia.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Ivan Banovac, Dora Sedmak, Monique Esclapez, Zdravko Petanjek
Summary: In this study, the molecular expression, morphological features, and laminar distribution of somatostatin cells in the human prefrontal cortex were comprehensively analyzed. The results showed that somatostatin neurons comprise around 7% of neocortical neurons, with different molecular and morphological characteristics in different cortical layers.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Yuji Odagaki, Masakazu Kinoshita, J. Javier Meana, Luis F. Callado, Jesus A. Garcia-Sevilla
Summary: The study found that the functional activation of G alpha(q/11) proteins coupled with 5-HT2A receptors and M-1 mAChRs in the prefrontal cortex is altered in opiate addicts compared to control subjects. This may contribute to addictive behavior towards opiates and neuropsychological consequences or comorbid mental disorders associated with opioid use.
PHARMACOLOGICAL REPORTS
(2021)
Article
Medicine, General & Internal
Alexander Gallo, Tim MacDonald, Kellie Bennett, Gioiamia Basso-Hulse, Gary Hulse
Summary: This study aimed to determine whether continuous low-dose flumazenil is anxiogenic like bolus doses. The results showed that there was no significant increase in state anxiety levels after continuous low-dose flumazenil infusion, and trait anxiety was significantly reduced one month after the treatment.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
N. A. Uranova, O. V. Vikhreva, V. I. Rakhmanova
Summary: This study aimed to investigate the abnormal interaction between neurons and satellite microglia (SatMg) in schizophrenia. Higher density of SatMg was found in the young schizophrenia group and those with shorter illness duration. The ultrastructural analysis revealed lower volume fraction and number of mitochondria, and higher volume fraction and number of lipofuscin granules and vacuoles in SatMg in schizophrenia. Neurons in schizophrenia showed larger soma area and vacuole volume compared to controls. The correlation between vacuoles in neurons and mitochondria in SatMg differed significantly between the control and schizophrenia group. These findings suggest disturbed SatMg-neuron interactions and mitochondrial abnormalities in SatMg as key factors in schizophrenia.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Article
Neurosciences
Kamyra S. Edokpolor, Anwesha Banerjee, Zachary T. McEachin, Jingsheng Gu, Adam Kosti, Juan D. Arboleda, Paul S. Garcia, Eric T. Wang, Gary J. Bassell
Summary: Considerable evidence suggests that loss of Muscleblind-like protein 2 (MBNL2) function in the brain is a major driver of central nervous system symptoms in Myotonic dystrophy type 1 (DM1). This study shows that MBNL2 depletion affects GABAergic function, which may explain the hypersomnia, fatigue, and surgical complications observed in DM1 patients.
Article
Clinical Neurology
Iria Brocos-Mosquera, Ane M. Gabilondo, J. Javier Meana, Luis F. Callado, Amaia M. Erdozain
Summary: Schizophrenia is associated with alterations in neurotransmission and synaptic dysfunction, with spinophilin protein expression showing a significant decrease in individuals with schizophrenia compared to controls. The study suggests that antipsychotic medications may produce alterations in spinophilin expression, potentially underlying some side effects of antipsychotics.
EUROPEAN NEUROPSYCHOPHARMACOLOGY
(2021)
Review
Psychiatry
Andrew J. Cutler, Gregory W. Mattingly, Vladimir Maletic
Summary: The pathophysiology of major depressive disorder is associated with impaired connectivity in key brain networks, which involves the GABAergic system of neurotransmission. Defects in GABA and neuroactive steroids (NASs) have been observed in adults with depression, and treatment with antidepressants can normalize these levels. There is interest in using NAS GABA(A) receptor positive allosteric modulators (PAMs) as potential treatments for depression, with brexanolone, zuranolone, and PH10 showing promise in clinical development. These NASs may provide novel and effective treatments for patients with major depressive disorder.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Ilias Chaibi, Mohamed Bennis, Saadia Ba-Mhamed
Summary: The study revealed the role of GABA-A receptor in the anterior cingulate cortex in regulating aggression, social, and anxiety-related behaviors in socially isolated mice. Muscimol increased these behaviors, while bicuculline reduced hyper-aggressive behavior and enhanced social behavior.
Article
Clinical Neurology
Brian Dean, Linh Q. Lam, Elizabeth Scarr, James A. Duce
JOURNAL OF AFFECTIVE DISORDERS
(2019)
Article
Psychiatry
Brian Dean, Andrew Tsatsanis, Linh Q. Lam, Elizabeth Scarr, James A. Duce
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2020)
Article
Neurosciences
Robin F. Chan, Gustavo Turecki, Andrey A. Shabalin, Jerry Guintivano, Min Zhao, Lin Y. Xie, Gerard van Grootheest, Zachary A. Kaminsky, Brian Dean, Brenda W. J. H. Penninx, Karolina A. Aberg, Edwin J. C. G. van den Oord
BIOLOGICAL PSYCHIATRY
(2020)
Article
Psychiatry
Andrew S. Gibbons, Daniel Hoyer, Brian Dean
Summary: A recent study found decreased mRNA expression of SMAD2 and SMAD4 in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia. Further investigation revealed lower levels of SMAD4 protein in the cortex of schizophrenia subjects, suggesting abnormalities in cortical TGFB-superfamily signalling in schizophrenia.
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
(2021)
Article
Neurosciences
Brian Dean, Georgia M. Parkin, Andrew S. Gibbons
EXPERIMENTAL BRAIN RESEARCH
(2020)
Article
Psychiatry
Kayoko Esaki, Shabeesh Balan, Yoshimi Iwayama, Chie Shimamoto-Mitsuyama, Yoshio Hirabayashi, Brian Dean, Takeo Yoshikawa
SCHIZOPHRENIA BULLETIN
(2020)
Article
Psychiatry
Brian Dean, Geoffrey Pavey, Elizabeth Scarr
SCHIZOPHRENIA RESEARCH
(2020)
Article
Neurosciences
Chie Shimamoto-Mitsuyama, Akihiro Nakaya, Kayoko Esaki, Shabeesh Balan, Yoshimi Iwayama, Tetsuo Ohnishi, Motoko Maekawa, Tomoko Toyota, Brian Dean, Takeo Yoshikawa
Summary: The study revealed lipid abnormalities in the corpus callosum of patients with schizophrenia and proposed the potential role of an impaired NFATC2-relevant gene network-microglial axis as its underlying mechanism.
Article
Psychiatry
Andrea Gogos, Jeehae Sun, Madhara Udawela, Andrew Gibbons, Maarten van den Buuse, Elizabeth Scarr, Brian Dean
Summary: The study found alterations in RAPGEF1 expression in the BA 8 of subjects with schizophrenia, but no differences in BA 8 and 44. Suicide completers had higher RAPGEF1 levels compared to non-suicide schizophrenia subjects in BA 8. Further investigation into the function of RAPGEF1 may provide insights into the pathophysiology of schizophrenia.
PSYCHIATRY RESEARCH
(2021)
Article
Clinical Neurology
Tamaki Ishima, Sebastian Illes, Yoshimi Iwayama, Brian Dean, Takeo Yoshikawa, Hans Agren, Keiko Funa, Kenji Hashimoto
Summary: The study found that BDNF mRNA expression was decreased in iPSC from bipolar disorder patients but increased in NSC, while BDNF-AS mRNA expression showed no changes between the two groups. Additionally, there was a significant decrease in BDNF mRNA expression in certain brain regions of bipolar disorder patients.
JOURNAL OF AFFECTIVE DISORDERS
(2021)
Article
Psychiatry
Brian Dean, Elizabeth Scarr
Summary: Studies show low levels of cortical muscarinic M1 receptors (CHRM1) in schizophrenia patients, affecting gene expression. Changes in cortical gene expression in Chrm1(-/-) mice are linked to schizophrenia pathology and Alzheimer's disease. Additionally, genes affected by CHRM1-mediated changes in gene expression are associated with cognitive ability in humans.
Article
Medicine, Research & Experimental
Winston Lee, Jana Zernant, Pei-Yin Su, Takayuki Nagasaki, Stephen H. Tsang, Rando Allikmets
Summary: This study provides a structured understanding of the genetic and clinical landscape of ABCA4 disease through genotype-phenotype correlation analysis, and adds a tool to quantitatively assess individual genotype-specific prognoses in patients.
Review
Psychiatry
Megan Snelleksz, Susan L. Rossell, Andrew Gibbons, Jess Nithianantharajah, Brian Dean
Summary: Research suggests that the frontal pole is significantly impacted in schizophrenia, with more gene expression changes compared to other brain regions. The frontal pole is essential for higher cognitive functions and has extensive connections with various brain regions. Dysfunction in the frontal pole plays a crucial role in the pathophysiology of schizophrenia, with structural, cellular, and molecular abnormalities contributing to the symptoms of the disorder.
PSYCHIATRY RESEARCH
(2022)
Article
Psychiatry
Brian Dean, Elizabeth H. X. Thomas, Kiymet Bozaoglu, Eric J. Tan, Tamsyn E. Van Rheenen, Erica Neill, Philip J. Sumner, Sean P. Carruthers, Elizabeth Scarr, Susan L. Rossell, Caroline Gurvich
Summary: Studying the working memory deficit phenotype within the syndrome of schizophrenia and its gene expression changes is significant for understanding the molecular pathology of the disorder and developing personalized medicine.
PSYCHIATRY RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Brian Dean
Summary: Schizophrenia is a syndrome that requires drugs targeting muscarinic M1 and M4 receptors, rather than dopamine D2 receptors, as antipsychotic drugs do. It would be ideal to identify individuals who respond to drugs activating the CHRM1 and 4 receptors, as non-response to treatment could be restricted to specific sub-groups within the syndrome.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2023)
