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NPJ Schizophrenia

Benedicto Crespo-Facorro, Carlos Prieto, Jesus Sainz
Antipsychotic drugs are one of the largest types of prescribed drugs. However, antipsychotic-induced weight gain (AIWG) is a major problem for the patients. AIWG increases cardiovascular and cerebrovascular morbidity and mortality, and reduces quality of life and drug compliance. To characterize changes in gene expression related to AIWG, we sequenced total messenger RNA from the blood samples of two groups of schizophrenia patients before and after 3 months of treatment with antipsychotics. The "weight gain" group was defined by an increase of body mass index (BMI) >1...
April 10, 2019: NPJ Schizophrenia
Alice Petty, Xiaoying Cui, Yasvir Tesiram, Deniz Kirik, Oliver Howes, Darryl Eyles
One of the most robust neurochemical abnormalities reported in patients living with schizophrenia is an increase in dopamine (DA) synthesis and release in the dorsal striatum (DS). Importantly, it appears that this increase progresses as a patient transitions from a prodromal stage to the clinical diagnosis of schizophrenia. Here we have recreated this pathophysiology in an animal model by increasing the capacity for DA synthesis preferentially within the DS. To achieve this we administer a genetic construct containing the rate-limiting enzymes in DA synthesis-tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) (packaged within an adeno-associated virus)-into the substantia nigra pars compacta (SNpc) of adolescent animals...
March 29, 2019: NPJ Schizophrenia
Vanessa Kiyomi Ota, Patricia Natalia Moretti, Marcos Leite Santoro, Fernanda Talarico, Leticia Maria Spindola, Gabriela Xavier, Carolina Muniz Carvalho, Diogo Ferri Marques, Giovany Oliveira Costa, Renata Pellegrino, Simone de Jong, Quirino Cordeiro, Hakon Hakonarson, Gerome Breen, Cristiano Noto, Rodrigo Affonseca Bressan, Ary Gadelha, Jair de Jesus Mari, Sintia I Belangero
The study of patients with schizophrenia (SZ) at different clinical stages may help clarify what effects could be due to the disease itself, to the pharmacological treatment, or to the disease progression. We compared expression levels of targeted genes in blood from individuals in different stages of SZ: clinical high risk for psychosis (CHR), first episode of psychosis (FEP), and chronic SZ (CSZ). Then, we further verified whether single-nucleotide polymorphisms (SNPs) could be related to gene expression differences...
March 28, 2019: NPJ Schizophrenia
Satoshi Okazaki, Ikuo Otsuka, Shusuke Numata, Tadasu Horai, Kentaro Mouri, Shuken Boku, Tetsuro Ohmori, Ichiro Sora, Akitoyo Hishimoto
The accelerated aging hypothesis of schizophrenia (SCZ) has been proposed. DNA methylation profiles were developed for determining "epigenetic age." Here, we assessed intrinsic and extrinsic epigenetic age acceleration (IEAA and EEAA, respectively) in SCZ. We examined two independent cohorts of Japanese ancestry. The first cohort consisted of 80 patients with SCZ under long-term or repeated hospitalization and 40 controls, with the economical DNA pooling technique. The second cohort consisted of 24 medication-free patients with SCZ and 23 controls...
February 27, 2019: NPJ Schizophrenia
Pavel Katsel, Panos Roussos, Peter Fam, Sonia Khan, Weilun Tan, Tetsuro Hirose, Shinichi Nakagawa, Mikhail V Pletnikov, Vahram Haroutunian
Oligodendrocyte (OLG)-related abnormalities have been broadly observed in schizophrenia (SZ); however, the etiology of these abnormalities remains unknown. As SZ is broadly believed to be a developmental disorder, the etiology of the myelin abnormalities in SZ may be related to OLG fate specification during development. Noncoding RNAs (ncRNAs) are an important part of multifaceted transcriptional complexes participating in neurogenic commitment and regulation of postmitotic cell function. The long ncRNA, NEAT1, is a structural component of paraspeckles (subnuclear bodies in interchromatin regions) that may control activity of developmental enhancers of OLG fate specification...
January 29, 2019: NPJ Schizophrenia
Sunil Vasu Kalmady, Russell Greiner, Rimjhim Agrawal, Venkataram Shivakumar, Janardhanan C Narayanaswamy, Matthew R G Brown, Andrew J Greenshaw, Serdar M Dursun, Ganesan Venkatasubramanian
In the literature, there are substantial machine learning attempts to classify schizophrenia based on alterations in resting-state (RS) brain patterns using functional magnetic resonance imaging (fMRI). Most earlier studies modelled patients undergoing treatment, entailing confounding with drug effects on brain activity, and making them less applicable to real-world diagnosis at the point of first medical contact. Further, most studies with classification accuracies >80% are based on small sample datasets, which may be insufficient to capture the heterogeneity of schizophrenia, limiting generalization to unseen cases...
January 18, 2019: NPJ Schizophrenia
Kourtney Graham, Jiajing Zhang, Haifa Qiao, Yuying Wu, Yi Zhou
The 14-3-3 family of proteins is genetically linked to several psychiatric disorders, including schizophrenia. Our 14-3-3 functional knockout (FKO) mice, as well as other 14-3-3 knockout models, have been shown to exhibit behavioral endophenotypes related to schizophrenia. While specific forebrain regions, such as the prefrontal cortex (PFC) and hippocampus (HP), have been implicated in schizophrenic pathophysiology, the role of these brain regions in the top-down control of specific schizophrenia-associated behaviors has not been examined...
January 14, 2019: NPJ Schizophrenia
Natalya A Uranova, Olga V Vikhreva, Valentina I Rakhmanova, Diana D Orlovskaya
Microglial activation has been proposed to be involved in the pathophysiology of schizophrenia (SCZ). We hypothesized that dystrophic alterations of oligodendrocytes previously reported in the prefrontal white matter in SCZ might be associated with microglial activation in the acute state of SCZ. White matter of the prefrontal cortex (BA10) was studied in post-mortem brain tissue from 21 SCZ cases and 20 normal controls. The SCZ group included 12 subjects with predominantly positive symptoms and 9 subjects with predominantly negative symptoms...
December 13, 2018: NPJ Schizophrenia
Natália Bezerra Mota, Mariano Sigman, Guillermo Cecchi, Mauro Copelli, Sidarta Ribeiro
Discourse varies widely with age, level of education, and psychiatric state. Word graphs have been recently shown to provide behavioral markers of formal thought disorders in psychosis (e.g., disorganized flow of ideas) and to track literacy acquisition in children with typical development. Here we report that a graph-theoretical computational analysis of verbal reports from subjects spanning 6 decades of age and 2 decades of education reveals asymptotic changes over time that depend more on education than age...
December 7, 2018: NPJ Schizophrenia
Gaelle Keromnes, Tom Motillon, Nathalie Coulon, Alain Berthoz, Foucaud Du Boisgueheneuc, Moritz Wehrmann, Brice Martin, Bérangère Thirioux, Olivier Bonnot, Romain Ridereau, Eric Bellissant, Dominique Drapier, David Levoyer, Nemat Jaafari, Sylvie Tordjman
Clinical observations suggest early self-consciousness disturbances in schizophrenia. A double mirror combining the images of two individuals sitting on each side of the mirror was used to study self-other differentiation in 12 individuals with early onset schizophrenia (EOS) and 15 individuals with adult onset schizophrenia (AOS) compared to 27 typically developing controls (TDC) matched on age and sex. The effects of intermodal sensory perception (visual-tactile and visual-kinesthetic) on self-other recognition were also studied...
November 28, 2018: NPJ Schizophrenia
Florian J Raabe, Sabrina Galinski, Sergi Papiol, Peter G Falkai, Andrea Schmitt, Moritz J Rossner
Postmortem studies in patients with schizophrenia (SCZ) have revealed deficits in myelination, abnormalities in myelin gene expression and altered numbers of oligodendrocytes in the brain. However, gaining mechanistic insight into oligodendrocyte (OL) dysfunction and its contribution to SCZ has been challenging because of technical hurdles. The advent of individual patient-derived human-induced pluripotent stem cells (hiPSCs), combined with the generation of in principle any neuronal and glial cell type, including OLs and oligodendrocyte precursor cells (OPCs), holds great potential for understanding the molecular basis of the aetiopathogenesis of genetically complex psychiatric diseases such as SCZ and could pave the way towards personalized medicine...
November 19, 2018: NPJ Schizophrenia
Igne Sinkeviciute, Marieke Begemann, Merel Prikken, Bob Oranje, Erik Johnsen, Wan U Lei, Kenneth Hugdahl, Rune A Kroken, Carina Rau, Jolien D Jacobs, Silvia Mattaroccia, Iris E Sommer
Cognitive impairment is a core feature of schizophrenia, which is predictive for functional outcomes and is, therefore, a treatment target in itself. Yet, literature on efficacy of different pharmaco-therapeutic options is inconsistent. This quantitative review provides an overview of studies that investigated potential cognitive enhancers in schizophrenia. We included pharmacological agents, which target different neurotransmitter systems and evaluated their efficacy on overall cognitive functioning and seven separate cognitive domains...
October 25, 2018: NPJ Schizophrenia
Richard Newton, Alice Rouleau, Anna-Greta Nylander, Jean-Yves Loze, Henrike K Resemann, Sara Steeves, Benedicto Crespo-Facorro
Schizophrenia is a debilitating psychiatric disorder and patients experience significant comorbidity, especially cognitive and psychosocial deficits, already at the onset of disease. Previous research suggests that treatment during the earlier stages of disease reduces disease burden, and that a longer time of untreated psychosis has a negative impact on treatment outcomes. A targeted literature review was conducted to gain insight into the definitions currently used to describe patients with a recent diagnosis of schizophrenia in the early course of disease ('early' schizophrenia)...
October 15, 2018: NPJ Schizophrenia
Sophie K Kirchner, Astrid Roeh, Jana Nolden, Alkomiet Hasan
The main objective of this review was to evaluate studies on the diagnosis, treatment, and course of schizotypal personality disorder and to provide a clinical guidance on the basis of that evaluation. A systematic search in the PubMed/MEDLINE databases was conducted. Two independent reviewers extracted and assessed the quality of the data. A total of 54 studies were eligible for inclusion: 18 were on diagnostic instruments; 22, on pharmacological treatment; 3, on psychotherapy; and 13, on the longitudinal course of the disease...
October 3, 2018: NPJ Schizophrenia
Derya Çokal, Gabriel Sevilla, William Stephen Jones, Vitor Zimmerer, Felicity Deamer, Maggie Douglas, Helen Spencer, Douglas Turkington, Nicol Ferrier, Rosemary Varley, Stuart Watson, Wolfram Hinzen
Formal thought disorder (FTD) is clinically manifested as disorganized speech, but there have been only few investigations of its linguistic properties. We examined how disturbance of thought may relate to the referential function of language as expressed in the use of noun phrases (NPs) and the complexity of sentence structures. We used a comic strip description task to elicit language samples from 30 participants with schizophrenia (SZ), 15 with moderate or severe FTD (SZ + FTD), and 15 minimal or no FTD (SZ-FTD), as well as 15 first-degree relatives of people with SZ (FDRs) and 15 neurotypical controls (NC)...
September 19, 2018: NPJ Schizophrenia
Wei Cheng, Lena Palaniyappan, Mingli Li, Keith M Kendrick, Jie Zhang, Qiang Luo, Zening Liu, Rongjun Yu, Wei Deng, Qiang Wang, Xiaohong Ma, Wanjun Guo, Susan Francis, Peter Liddle, Andrew R Mayer, Gunter Schumann, Tao Li, Jianfeng Feng
No abstract text is available yet for this article.
September 17, 2018: NPJ Schizophrenia
David M Bortz, Anthony A Grace
The medial septum (MS) differentially impacts midbrain dopamine (DA) neuron activity via the ventral hippocampus, a region implicated in DA-related disorders. However, whether MS regulation of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is disrupted in a developmental disruption model of schizophrenia is unknown. Male Sprague-Dawley rats were exposed at gestational day 17 to methylazoxymethanol (MAM) or saline. As adults, NMDA (0.75 µg/0.2 µL) was infused into the MS, and either DA neuron activity in the VTA and SNc (7-9 anesthetized rats per group) or amphetamine-induced hyperlocomotion (AIH, 11-13 rats per group) was measured...
September 3, 2018: NPJ Schizophrenia
M P Boks, L C Houtepen, Z Xu, Y He, G Ursini, A X Maihofer, P Rajarajan, Q Yu, H Xu, Y Wu, S Wang, J P Shi, H E Hulshoff Pol, E Strengman, B P F Rutten, A E Jaffe, J E Kleinman, D G Baker, E M Hol, S Akbarian, C M Nievergelt, L D De Witte, C H Vinkers, D R Weinberger, J Yu, R S Kahn
Epigenetic changes may account for the doubled risk to develop schizophrenia in individuals exposed to famine in utero. We therefore investigated DNA methylation in a unique sample of patients and healthy individuals conceived during the great famine in China. Subsequently, we examined two case-control samples without famine exposure in whole blood and brain tissue. To shed light on the causality of the relation between famine exposure and DNA methylation, we exposed human fibroblasts to nutritional deprivation...
August 21, 2018: NPJ Schizophrenia
Abeer R Al-Shammari, Sanjeev K Bhardwaj, Ksenia Musaelyan, Lalit K Srivastava, Francis G Szele
Schizophrenia is a neurodevelopmental disorder likely caused by environmental and genetic risk factors but functional interactions between the risk factors are unclear. We tested the hypothesis that dysbindin-1 (Dtnbp1) gene mutation combined with postnatal exposure to viral mimetic polyI:C results in schizophrenia-related behavioural changes in adulthood, and mediates polyI:C-induced inflammation in the subventricular zone (SVZ). Adult Sandy (Sdy, Dtnbp1 mutant) mice given early postnatal polyI:C injections displayed reduced prepulse inhibition of startle, reduced locomotion and deficits in novel object recognition...
July 23, 2018: NPJ Schizophrenia
Xue Zou, Yiwen Zhu, John W Jackson, Andrea Bellavia, Garrett M Fitzmaurice, Franca Centorrino, Linda Valeri
To date, no study has evaluated the joint role of symptoms and adverse events as mediators of the effect of second-generation antipsychotics on patients' social functioning. We used recently developed methods for mediation analysis with multiple mediators to clarify the interplay of adverse events and symptoms in explaining the effects of paliperidone (R code for implementing the mediation analysis for multiple mediators is provided). We used data from 490 participants in a 6-week randomized dose-response trial that assigned three fixed dosages of ER OROS paliperidone (3, 9, and 15 mg/day)...
June 27, 2018: NPJ Schizophrenia
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