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Neuroscience: CNS disease, pain, brain research, ion channels, synaptic transmission, channelopathies, neuronal network
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Deficits in Predictive Coding Underlie Hallucinations in Schizophrenia

The neural mechanisms that produce hallucinations and other psychotic symptoms remain unclear. Previous research suggests that deficits in predictive signals for learning, such as prediction error signals, may underlie psychotic symptoms, but the mechanism by which such deficits produce psychotic symptoms remains to be established. We used model-based fMRI to study sensory prediction errors in human patients with schizophrenia who report daily auditory verbal hallucinations (AVHs) and sociodemographically matched healthy control subjects. We manipulated participants' expectations for hearing speech at different periods within a speech decision-making task. Patients activated a voice-sensitive region of the auditory cortex while they experienced AVHs in the scanner and displayed a concomitant deficit in prediction error signals in a similar portion of auditory cortex. This prediction error deficit correlated strongly with increased activity during silence and with reduced volumes of the auditory cortex, two established neural phenotypes of AVHs. Furthermore, patients with more severe AVHs had more deficient prediction error signals and greater activity during silence within the region of auditory cortex where groups differed, regardless of the severity of psychotic symptoms other than AVHs. Our findings suggest that deficient predictive coding accounts for the resting hyperactivity in sensory cortex that leads to hallucinations. (...) -  by Horga et al., The Journal of Neuroscience, 11 June 2014, 34(24): 8072-8082

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Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia

Age-Dependent MicroRNA Control of Synaptic Plasticity in 22q11 Deletion Syndrome and Schizophrenia | Neuroscience_topics | Scoop.it

The 22q11 deletion syndrome (22q11DS) is characterized by multiple physical and psychiatric abnormalities and is caused by the hemizygous deletion of a 1.5–3 Mb region of chromosome 22. It constitutes one of the strongest known genetic risks for schizophrenia; schizophrenia arises in as many as 30% of patients with 22q11DS during adolescence or early adulthood. A mouse model of 22q11DS displays an age-dependent increase in hippocampal long-term potentiation (LTP), a form of synaptic plasticity underlying learning and memory. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2), which is responsible for loading Ca2+ into the endoplasmic reticulum (ER), is elevated in this mouse model. The resulting increase in ER Ca2+ load leads to enhanced neurotransmitter release and increased LTP. However, the mechanism by which the 22q11 microdeletion leads to SERCA2 overexpression and LTP increase has not been determined. Screening of multiple mutant mouse lines revealed that haploinsufficiency of Dgcr8, a microRNA (miRNA) biogenesis gene in the 22q11DS disease-critical region, causes age-dependent, synaptic SERCA2 overexpression and increased LTP. We found that miR-25 and miR-185, regulators of SERCA2, are depleted in mouse models of 22q11DS. Restoration of these miRNAs to presynaptic neurons rescues LTP in Dgcr8+/− mice. Finally, we show that SERCA2 is elevated in the brains of patients with schizophrenia, providing a link between mouse model findings and the human disease. We conclude that miRNA-dependent SERCA2 dysregulation is a pathogenic event in 22q11DS and schizophrenia. - by Earls LR et al., The Journal of Neuroscience, 10 October 2012, 32(41): 14132-14144

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From antipsychotic to anti-schizophrenia drugs: role of animal models

Current drugs for treating schizophrenia are mostly variations on a theme that was started over 50 years ago. Sadly, clinical efficacy has not improved substantially over the years. We argue that both clinical and preclinical researchers have focused too much on psychosis, which is only one of the hallmarks of schizophrenia. This narrow focus has hampered the development of relevant animal models and human experimental medicine paradigms. Other fields in psychiatry, most notably in the realms of addiction and anxiety, have prospered from results obtained in parallel studies using animal models and experimental human studies. Lessons to be learned from those models and recent genetic and cognitive insights in schizophrenia can be utilized to develop better animal and human models and, potentially, novel treatment strategies. (...) - by Geyer MA et al, Trends in Pharmacological Sciences, Volume 33, Issue 10, October 2012, Pages 515–521

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Trends in Pharmacological Sciences - From antipsychotic to anti-schizophrenia drugs: role of animal models

Trends in Pharmacological Sciences - From antipsychotic to anti-schizophrenia drugs: role of animal models | Neuroscience_topics | Scoop.it

[Abstract] Current drugs for treating schizophrenia are mostly variations on a theme that was started over 50 years ago. Sadly, clinical efficacy has not improved substantially over the years. We argue that both clinical and preclinical researchers have focused too much on psychosis, which is only one of the hallmarks of schizophrenia. This narrow focus has hampered the development of relevant animal models and human experimental medicine paradigms. Other fields in psychiatry, most notably in the realms of addiction and anxiety, have prospered from results obtained in parallel studies using animal models and experimental human studies. Lessons to be learned from those models and recent genetic and cognitive insights in schizophrenia can be utilized to develop better animal and human models and, potentially, novel treatment strategies. - by Geyer MA et al.Trends in Pharmacological SciencesVolume 33, Issue 10, 515-521, 17 July 2012

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Keely Contadeluci's curator insight, April 2, 2013 10:06 AM

Good for IB Bio LOA principles and ethics.

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New de novo Genetic Mutations in Schizophrenia Identified

New de novo Genetic Mutations in Schizophrenia Identified | Neuroscience_topics | Scoop.it

Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease. The study, the largest and most comprehensive of its kind, was published today in the online edition of the journal Nature Genetics

Although schizophrenia typically onsets during adolescence and early adulthood, many of the mutations were found to affect genes with higher expression during early-to-mid fetal development. Together, the findings show that both the function of the mutated gene and when the gene is expressed are critically important in determining the risk for schizophrenia. (...) - Neuroscience News, October 3, 2012

Original article: "De novo gene mutations highlight patterns of genetic and neural complexity in schizophrenia" , by Xu B et al., Nature Genetics, Published online 03 October 2012

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Arielle Gold's curator insight, November 24, 2014 3:48 PM

This article discusses a study that was conducted by scientists in order to have a better understanding of the mutations that cause Schizophrenia (Xu et al., 2012). The article discusses that these mutations commonly occur when a fetus is developing in the womb (Xu et al., 2012),  and can be caused by various infections or viruses. This concept is also discussed in the "Exploring Psychology in Modules" textbook, written by David G. Myers (Myers & Myers, 2008). Through comparing the exomes; parts of the genetic material of an individual that consist of the coding portions of genes, of individuals who do not have schizophrenia with those of their parents who also had no relation to the disorder, scientists were able to come to the conclusion that there is no specific brain mutation that is responsible for causing or increasing the chances of an individual having Schizophrenia (Xu et al., 2012). There are countless different mutations that can increase an individual's chance of getting this mental disorder, which can be scary to think about, however, this study seems to have given scientists a better understanding of Schizophrenia than they have ever had before. Because of this, chances are that in the near future, psychological scientists may be able to better predict the onset of Schizophrenia in a patient, and ideally prevent it from happening altogether.

 

This research is valuable for people of all ages and genders, particularly those who have Schizophrenia, because it shows them that people are working hard to find a cure, and gives them hope that the cure will be found in the near future (Xu et al., 2012). The information in this article appears to be reliable and accurate because it is well-written, and the contributors are listed at the bottom (Xu et al., 2012). These contributors appear to be well-educated because the majority of them work for the Columbia University Medical Center (Xu et al., 2012), which seems to be a well-renowned medical facility. The scientific explanations in this article were thorough and described in detail, and were based on information provided by accurate sources (Xu et al., 2012). 

 

The following is the full-text reference of the textbook that was briefly mentioned in my evaluation of this article, along with the citation of the article itself:

 

Myers, D. G., & Myers, D. G. (2008). Schizophrenia. In Exploring Psychology in Modules(9th ed., pp. 562-568). Retrieved from http://books.google.com/books?id=ReckAAAAQBAJ&printsec=frontcover&authuser=2&source=gbs_ge_summary_r&hl=en&output=reader&pg=GBS.PA568

 

Xu, B., Ionata-Laza, I., Louw Roos, J., Boone, B., Woodrick, S., Sun, Y., & Levy, S. (2012, October 3). "New De Novo Genetic Mutations in Schizophrenia Identified" - Neuroscience News. Retrieved from http://neurosciencenews.com/new-de-novo-genetic-mutations-in-schizophrenia-identified/

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Another view of the history of antipsychotic drug discovery and development

Another view of the history of antipsychotic drug discovery and development | Neuroscience_topics | Scoop.it

Chlorpromazine initiated effective pharmacotherapy for schizophrenia 60 years ago. This discovery initiated or stimulated key developments in the field of psychiatry. Nonetheless, advances in pharmacotherapy of schizophrenia have been modest. Psychosis remains the primary aspect of psychopathology addressed, and core pathologies such as cognition and negative symptom remain unmet therapeutic challenges. New clinical and basic neuroscience paradigms may guide the near future and provide a more heuristic construct for novel and innovative discovery. By Carpenter WT & Davis JMMolecular Psychiatry advance online publication 14 August 2012

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