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Understanding schizophrenia

Elizabeth P Lackey, Detlef H Heck, Roy V Sillitoe
The cerebellum is the focus of an emergent series of debates because its circuitry is now thought to encode an unexpected level of functional diversity. The flexibility that is built into the cerebellar circuit allows it to participate not only in motor behaviors involving coordination, learning, and balance but also in non-motor behaviors such as cognition, emotion, and spatial navigation. In accordance with the cerebellum's diverse functional roles, when these circuits are altered because of disease or injury, the behavioral outcomes range from neurological conditions such as ataxia, dystonia, and tremor to neuropsychiatric conditions, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder...
2018: F1000Research
Maria Azmanova, Anaïs Pitto-Barry, Nicolas P E Barry
Schizophrenia is a complex and unpredictable mental disorder which affects several domains of cognition and behaviour. It is a heterogeneous illness characterised by positive, negative, and cognitive symptoms, often accompanied by signs of depression. In this tutorial review, we discuss recent progress in understanding the target sites and mechanisms of action of second-generation antipsychotic drugs. Progress in identifying and defining target sites has been accelerated recently by advances in neuroscience, and newly developed agents that regulate signalling by the main excitatory neurotransmitters in the brain are surveyed...
May 1, 2018: MedChemComm
Luciana López-Jury, Rodrigo C Meza, Matthew T C Brown, Pablo Henny, Carmen C Canavier
Action potentials (APs) in nigral dopaminergic neurons often exhibit two separate components, the first reflecting spike initiation in the dendritically located axon initial segment (AIS) and the second the subsequent dendro-somatic spike. These components are separated by a notch in the ascending phase of the somatic extracellular waveform and in the temporal derivative of the somatic intracellular waveform. Still, considerable variability exists in the presence and magnitude of the notch across neurons. To systematically address the contribution of AIS, dendritic and somatic compartments to shaping the two-component APs, we modeled APs of previously in vivo electrophysiologically characterized and 3D-reconstructed male mouse and rat dopaminergic neurons...
August 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Britta Hahn, Benjamin M Robinson, Carly J Leonard, Steven J Luck, James M Gold
Prefrontal cortex (PFC) dysfunction is widely believed to underlie working memory (WM) deficits in people with schizophrenia (PSZ), but few studies have focused on measures of WM storage devoid of manipulation. Research in neurotypical individuals has shown that storage capacity is more closely related to posterior parietal cortex (PPC) than PFC, suggesting that reductions in WM storage capacity in schizophrenia that are associated with broad cognitive deficits may be related to neural activity in PPC. In the present human neuroimaging study, 37 PSZ and 37 matched healthy control subjects (HCS) of either sex completed a change detection task with varying set sizes while undergoing functional Magnetic Resonance Imaging...
August 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Cecilia Brain, Steven Kymes, Dana B DiBenedetti, Thomas Brevig, Dawn I Velligan
BACKGROUND: Treatment-resistant schizophrenia (TRS) affects about one-third of individuals with schizophrenia. People with TRS do not experience sustained symptom relief and at the same time have the most severe disease-related disability and associated costs among individuals with severe mental disorders. Like caregivers of people with treatment-responsive schizophrenia, caregivers of individuals with TRS experience the disease burden along with their care recipients; however, for those providing care for individuals with TRS, the stress of the burden is unrelenting due to uncontrolled symptoms and a lack of effective treatment options...
August 13, 2018: BMC Psychiatry
Daniel G Amen, Sachit Egan, Somayeh Meysami, Cyrus A Raji, Noble George
BACKGROUND: Understanding the influence of aging on the brain remains a challenge in determining its role as a risk factor for Alzheimer's disease. OBJECTIVE: To identify patterns of aging in a large neuroimaging cohort. METHODS: A large psychiatric cohort of 31,227 individuals received brain SPECT at rest and during a concentration task for a total of 62,454 scans. ANOVA was done to identify the mean age trends over the course of the age range in this group, 0- 105 years...
August 3, 2018: Journal of Alzheimer's Disease: JAD
Hiroaki Hori, Seiji Nakamura, Fuyuko Yoshida, Toshiya Teraishi, Daimei Sasayama, Miho Ota, Kotaro Hattori, Yoshiharu Kim, Teruhiko Higuchi, Hiroshi Kunugi
Etiology of depression and its vulnerability remains elusive. Using a latent profile analysis on dimensional personality traits, we previously identified 3 different phenotypes in the general population, namely stress-resilient, -vulnerable, and -resistant groups. Here we performed microarray-based blood gene expression profiling of these 3 groups (n = 20 for each group) in order to identify genes involved in stress vulnerability as it relates to the risk of depression. Identified differentially expressed genes among the groups were most markedly enriched in ribosome-related pathways...
August 6, 2018: Journal of Psychiatric Research
Lorena Oliveira de Matos, Ana Luiza de Araujo Lima Reis, Lorena Terene Lopes Guerra, Leonardo de Oliveira Guarnieri, Muiara Aparecida Moraes, Nayara Soares Sena Aquino, Raphael E Szawka, Grace Schenatto Pereira, Bruno Rezende Souza
Alterations in dopaminergic signaling and neurodevelopment are associated with many neuropsychiatric disorders, such as attention deficit and hyperactivity disorder (ADHD), autism, and schizophrenia. Imbalances in dopamine levels during prenatal development are associated with behavioral alterations later in life, like hyperactivity and addiction, and it is possible that dopaminergic imbalances may have diverse effects during different neurodevelopmental windows. In this study, we investigate whether an increase in dopamine levels during the perinatal developmental window affects behavior of juvenile male and female Swiss mice...
August 10, 2018: Pharmacology, Biochemistry, and Behavior
Michael de Ridder, Karsten Klein, Jean Yang, Pengyi Yang, Jim Lagopoulos, Ian Hickie, Max Bennett, Jinman Kim
Analysis and interpretation of functional magnetic resonance imaging (fMRI) has been used to characterise many neuronal diseases, such as schizophrenia, bipolar disorder and Alzheimer's disease. Functional connectivity networks (FCNs) are widely used because they greatly reduce the amount of data that needs to be interpreted and they provide a common network structure that can be directly compared. However, FCNs contain a range of data uncertainties stemming from inherent limitations, e.g. during acquisition, as well as the loss of voxel-level data, and the use of thresholding in data abstraction...
August 11, 2018: Neuroinformatics
Giulia Boscutti, Eugenii A Rabiner, Christophe Plisson
The development of β+ emitter tracers labelled with carbon-11 or fluorine-18 having optimal characteristics of affinity and selectivity for the phosphodiesterase 10 A protein has received considerable attention, due to the major implication of this enzyme in neurological and psychiatric disorders, such as Hungtington's disease, Parkinson's disease and schizophrenia. The ability to quantify PDE10 A availability in the human brain in vivo will thus aid understanding its role in neurodegenerative and neuropsychiatric pathophysiology as well as providing a valuable tool for drug development...
August 9, 2018: Neuroscience Letters
Aaron Carass, Jennifer L Cuzzocreo, Shuo Han, Carlos R Hernandez-Castillo, Paul E Rasser, Melanie Ganz, Vincent Beliveau, Jose Dolz, Ismail Ben Ayed, Christian Desrosiers, Benjamin Thyreau, José E Romero, Pierrick Coupé, José V Manjón, Vladimir S Fonov, D Louis Collins, Sarah H Ying, Chiadi U Onyike, Deana Crocetti, Bennett A Landman, Stewart H Mostofsky, Paul M Thompson, Jerry L Prince
The human cerebellum plays an essential role in motor control, is involved in cognitive function (i.e., attention, working memory, and language), and helps to regulate emotional responses. Quantitative in-vivo assessment of the cerebellum is important in the study of several neurological diseases including cerebellar ataxia, autism, and schizophrenia. Different structural subdivisions of the cerebellum have been shown to correlate with differing pathologies. To further understand these pathologies, it is helpful to automatically parcellate the cerebellum at the highest fidelity possible...
August 9, 2018: NeuroImage
Elyse J Cadena, David M White, Nina V Kraguljac, Meredith A Reid, Ripu Jindal, Roland Matthew Pixley, Adrienne C Lahti
To better understand cognitive control impairment in schizophrenia, it is vital to determine the extent of dysfunctional connectivity in the associated fronto-striatal brain network, with a focus on the connections with the anterior cingulate cortex (ACC), prior to the potential confounding effect of medication. It is also essential to determine the effects following antipsychotic medication and the relationship of those effects on psychosis improvement. Twenty-two patients with schizophrenia, initially unmedicated and after a 6-week course of risperidone, and 20 matched healthy controls (HC) performed a fMRI task twice, six weeks apart...
August 8, 2018: Schizophrenia Research
Teresa Katthagen, Christoph Mathys, Lorenz Deserno, Henrik Walter, Norbert Kathmann, Andreas Heinz, Florian Schlagenhauf
In schizophrenia, increased aberrant salience to irrelevant events and reduced learning of relevant information may relate to an underlying deficit in relevance detection. So far, subjective estimates of relevance have not been probed in schizophrenia patients. The mechanisms underlying belief formation about relevance and their translation into decisions are unclear. Using novel computational methods, we investigated relevance detection during implicit learning in 42 schizophrenia patients and 42 healthy individuals...
August 10, 2018: PLoS Computational Biology
Ruta Samanaite, Amy Gillespie, Kyra-Verena Sendt, Grant McQueen, James H MacCabe, Alice Egerton
Background: Clozapine is the recommended antipsychotic for treatment-resistant schizophrenia (TRS) but there is significant variability between patients in the degree to which clozapine will improve symptoms. The biological basis of this variability is unknown. Although clozapine has efficacy in TRS, it can elicit adverse effects and initiation is often delayed. Identification of predictive biomarkers of clozapine response may aid initiation of clozapine treatment, as well as understanding of its mechanism of action...
2018: Frontiers in Psychiatry
Jibi A Jacob, Anju Kuruvilla
Background: Patients with schizophrenia hold a variety of explanatory models of illness that influence different aspects of their life including their understanding of the disease, ability to cope and sense of well-being. Aim: To study the association of explanatory models and quality of life in patients with schizophrenia. Materials and Methods: One hundred and thirty consecutive patients with schizophrenia attending a psychiatric outpatient clinic were recruited in the study and administered the Positive and Negative Symptom Scale (PANSS), the modified Short Explanatory Model Interview (SEMI) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) Scale to assess severity of psychosis, explanatory models of illness, and quality of life...
July 2018: Indian Journal of Psychological Medicine
Steven M Silverstein, Docia L Demmin, James A Bednar
Computational modeling is a useful method for generating hypotheses about the contributions of impaired neurobiological mechanisms, and their interactions, to psychopathology. Modeling is being increasingly used to further our understanding of schizophrenia, but to date, it has not been applied to questions regarding the common perceptual disturbances in the disorder. In this article, we model aspects of low-level visual processing and demonstrate how this can lead to testable hypotheses about both the nature of visual abnormalities in schizophrenia and the relationships between the mechanisms underlying these disturbances and psychotic symptoms...
December 2017: Computational psychiatry
Hannah J Jones, Jon Heron, Gemma Hammerton, Jan Stochl, Peter B Jones, Mary Cannon, George Davey Smith, Peter Holmans, Glyn Lewis, David E J Linden, Michael C O'Donovan, Michael J Owen, James Walters, Stanley Zammit
Whilst associations between polygenic risk scores (PRSs) for schizophrenia and various phenotypic outcomes have been reported, an understanding of developmental pathways can only be gained by modelling comorbidity across psychopathology. We examine how genetic risk for schizophrenia relates to adolescent psychosis-related and internalizing psychopathology using a latent modelling approach, and compare this to genetic risk for other psychiatric disorders, to gain a more comprehensive understanding of the developmental pathways at this age...
August 8, 2018: Translational Psychiatry
Alexandre Bacq, Simone Astori, Elias Gebara, Wei Tang, Bianca A Silva, Jose Sanchez-Mut, Jocelyn Grosse, Isabelle Guillot de Suduiraut, Olivia Zanoletti, Catherine Maclachlan, Graham W Knott, Johannes Gräff, Carmen Sandi
Aggression is frequently observed in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Due to a lack of understanding of its underlying mechanisms, effective treatments for abnormal aggression are still missing. Recently, genetic variations in Sialyltransferase 2 (St8sia2) have been linked to these disorders and aggression. Here we identify abnormal aggressive behaviors and concomitant blunted fear learning in St8sia2 knockout (-/-) mice. It is worth noting that the amygdala of St8sia2-/- mice shows diminished threat-induced activation, as well as alterations in synaptic structure and function, including impaired GluN2B-containing NMDA receptor-mediated synaptic transmission and plasticity...
August 8, 2018: Molecular Psychiatry
Ahmet S Ozcan, Mehmet S Ozcan
Structural plasticity, characterized by the formation and elimination of synapses, plays a big role in learning and long-term memory formation in the brain. The majority of the synapses in the neocortex occur between the axonal boutons and dendritic spines. Therefore, understanding the dynamics of the dendritic spine growth and elimination can provide key insights to the mechanisms of structural plasticity. In addition to learning and memory formation, the connectivity of neural networks affects cognition, perception, and behavior...
2018: Frontiers in Synaptic Neuroscience
Maria Fjellvang, Linda Grøning, Unn K Haukvik
Background: Persons with schizophrenia have a small but significant increase in risk of violence, which remains after controlling for known environmental risk factors. In vivo MRI-studies may point toward the biological underpinnings of psychotic violence, and neuroimaging has increasingly been used in forensic and legal settings despite unclear relevance. Objectives: (1) To present the first systematic review, following standardized guidelines, of MRI studies of violence with schizophrenia. (2) To critically discuss the promises and pitfalls of using this literature to understand violence in schizophrenia in clinical, forensic, and legal settings...
2018: Frontiers in Psychiatry
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