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Schizophrenia etiology

A Büki, G Horvath, G Benedek, E Ducza, G Kekesi
After peri-adolescence isolation rearing (IS) and subchronic ketamine (KET) treatment, adult, selectively bred Wistar rats (named WISKET) mimic abnormal behaviors reminiscent of human schizophrenia, including reduced prepulse-inhibition of startle reflex, disturbances in cognition, locomotor activity and thermoregulation, decreased pain sensitivity and electrophysiological alterations. To further validate our WISKET rat line, regarding its translational utility in schizophrenia research, we examined their social behavior and introduced a short and simple holeboard-like test to investigate their motivational deficit that predicts the cognitive disturbance...
July 27, 2018: Genes, Brain, and Behavior
Ebba Du Rietz, Jonathan Coleman, Kylie Glanville, Shing Wan Choi, Paul F O'Reilly, Jonna Kuntsi
BACKGROUND: A recent large-scale mega genome-wide association study identified, for the first time, genetic variants at 12 loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). In this study we use a powerful polygenic approach, with polygenic scores derived from the genome-wide association study, to investigate the etiological overlap between ADHD and frequently co-occurring traits and disorders. METHODS: Polygenic risk scores for ADHD derived from the mega genome-wide association study (20,183 cases and 35,191 control subjects) were computed in a large-scale adult population sample (N = 135,726) recruited by the UK Biobank...
July 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Kazuo Kunisawa, Takeshi Shimizu, Itaru Kushima, Branko Aleksic, Daisuke Mori, Yasuyuki Osanai, Kenta Kobayashi, Anna M Taylor, Manzoor A Bhat, Akiko Hayashi, Hiroko Baba, Norio Ozaki, Kazuhiro Ikenaka
Myelinated axons segregate the axonal membrane into four defined regions: the node of Ranvier, paranode, juxtaparanode and internode. The paranodal junction consists of specific component proteins, such as neurofascin155 (NF155) on the glial side, and Caspr and Contactin on the axonal side. Although paranodal junctions are thought to play crucial roles in rapid saltatory conduction and nodal assembly, the role of their interaction with neurons is not fully understood. In a previous study, conditional NF155 knockout in oligodendrocytes led to disorganization of the paranodal junctions...
July 19, 2018: Journal of Neurochemistry
Amy T Peters, Sally M Weinstein, Ashley Isaia, Anna VAN Meter, Courtney A Zulauf, Amy E West
BACKGROUND: Accurate assessment of pediatric bipolar disorder (BD) is important for allocating appropriate treatment, but it is complicated by significant heterogeneity in symptom presentation and high rates of comorbidity. Investigating clinical subtypes of the disorder may help to clarify diagnostic boundaries and inform targeted treatment. This study used a full diagnostic instrument to examine symptom patterns among youth with BD. METHOD: Trained interviewers completed the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with 71 children (7 to 13 y of age) and families as part of the baseline assessment for a randomized clinical trial of Child- and Family-focused Cognitive-Behavioral Therapy (CFF-CBT) compared with treatment as usual (TAU) for pediatric BD...
May 2018: Journal of Psychiatric Practice
Rigil K Yeung, Zheng-Hua Xiang, Shui-Ying Tsang, Rui Li, Timothy Y C Ho, Qi Li, Chok-King Hui, Pak-Chung Sham, Ming-Qi Qiao, Hong Xue
Intronic polymorphisms of the GABAA receptor β2 subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure...
July 17, 2018: Translational Psychiatry
Ari B Cuperfain, Zhi Lun Zhang, James L Kennedy, Vanessa F Gonçalves
While accounting for only 2% of the body's weight, the brain utilizes up to 20% of the body's total energy. Not surprisingly, metabolic dysfunction and energy supply-and-demand mismatch have been implicated in a variety of neurological and psychiatric disorders. Mitochondria are responsible for providing the brain with most of its energetic demands, and the brain uses glucose as its exclusive energy source. Exploring the role of mitochondrial dysfunction in the etiology of psychiatric disease is a promising avenue to investigate further...
June 2018: Molecular Neuropsychiatry
Joanna Szczotka, Bartosz Majchrowicz
Theories of schizophrenia propose numerous mechanisms underlying development of this disorder, yet the account including satisfactory etiological explanation is still lacking. Current trend is to indicate core, basic factors which may further give rise to whole diversity of symptoms. Experimental data and patients' reports show that such key factor may be selfexperience disturbed on a basic, pre-reflective level, which can then lead to many higher-order symptoms. In this article we review and analyze these data, as well as the most influential cognitive theories focusing on mechanisms influencing the clinical picture of schizophrenia and giving rise to the anomalous experience of embodied self...
April 30, 2018: Psychiatria Polska
Kally C O'Reilly, Eliott R J Levy, Alejandra V Patino, Maria I Perica, André A Fenton
Patients with neuropsychiatric and neurological disorders often express limbic circuit abnormalities and deficits in information processing. While these disorders appear to have diverse etiologies, their common features suggest neurodevelopmental origins. Neurodevelopment is a prolonged process of diverse events including neurogenesis/apoptosis, axon pathfinding, synaptogenesis, and pruning, to name a few. The precise timing of the neurodevelopmental insult to these processes likely determines the resulting functional outcome...
June 27, 2018: Brain Structure & Function
Marsha A Wilcox, Adam J Savitz, Anjené M Addington, Gary S Gray, Eva C Guinan, John W Jackson, Thomas Lehner, Sharon-Lise Normand, Hardeep Ranu, Geetha Senthil, Jake Spertus, Linda Valeri, Joseph S Ross
Clinical trial data are the gold standard for evaluating pharmaceutical safety and efficacy. There is an ethical and scientific imperative for transparency and data sharing to confirm published results and generate new knowledge. The Open Translational Science in Schizophrenia (OPTICS) Project was an open-science initiative aggregating Janssen clinical trial and NIH/NIMH data from real-world studies and trials in schizophrenia. The project aims were to show the value of using shared data to examine: therapeutic safety and efficacy; disease etiologies and course; and methods development...
June 27, 2018: NPJ Schizophrenia
Marc De Hert, Johan Detraux, Davy Vancampfort
Coronary heart disease (CHD) and mental illness are among the leading causes of morbidity and mortality worldwide. Decades of research has revealed several, and sometimes surprising, links between CHD and mental illness, and has even suggested that both may actually cause one another. However, the precise nature of these links has not yet been clearly established. The goal of this paper, therefore, is to comprehensively review and discuss the state-of-the-art nature of the epidemiological and pathophysiological aspects of the bidirectional links between mental illness and CHD...
March 2018: Dialogues in Clinical Neuroscience
P Vasileiadis, G Mavridis, A Keramidas, D Chardalidou, I Pervos, C Charalampous
BACKGROUND: Chilaiditi's sign is defined as the interposition of bowels between the liver and the right diaphragm. When the patient is symptomatic due to the intestinal obstruction, the case is referred to as Chilaiditi's syndrome. OBJECTIVE: To emphasize the importance of accurate diagnose of Chilaiditi's syndrome in patients with psychotic disturbances. METHOD: A 46 years old male was admitted to our department suffering from a constant epigastric and right upper quadrant pain with radiation to the right shoulder...
June 26, 2018: Clinical Schizophrenia & related Psychoses
Anna A Igolkina, Chris Armoskus, Jeremy R B Newman, Oleg V Evgrafov, Lauren M McIntyre, Sergey V Nuzhdin, Maria G Samsonova
Schizophrenia (SCZ) is a psychiatric disorder of unknown etiology. There is evidence suggesting that aberrations in neurodevelopment are a significant attribute of schizophrenia pathogenesis and progression. To identify biologically relevant molecular abnormalities affecting neurodevelopment in SCZ we used cultured neural progenitor cells derived from olfactory neuroepithelium (CNON cells). Here, we tested the hypothesis that variance in gene expression differs between individuals from SCZ and control groups...
2018: Frontiers in Molecular Neuroscience
Ai Koyanagi, Hans Oh, Andrew Stickley, Brendon Stubbs, Nicola Veronese, Davy Vancampfort, Josep Maria Haro, Jordan E DeVylder
BACKGROUND: Sibship size and birth order may be contributing factors to the multifactorial etiology of psychosis. Specifically, several studies have shown that sibship size and birth order are associated with schizophrenia. However, there are no studies on their association with psychotic experiences (PE). METHODS: Cross-sectional, community-based data from 43 low- and middle-income countries which participated in the World Health Survey were analyzed. The Composite International Diagnostic Interview was used to identify four types of past 12-month PE...
June 18, 2018: Schizophrenia Research
Michele Poletti, Andrea Raballo
The Polygenic Risk Scores (PRS) approach is becoming increasingly prominent in psycho-behavioral research, however, its translational potential is still relatively underconceptualized. Indeed, PRS paradigm (which capitalizes on the combination of multiple genetic markers into a single proxy score to predict lifetime outcomes) has the potential to unravel some of the developmental complexities leading to severe mental disorders. With respect to schizophrenia, the application of PRS approach to child-adolescent cohorts from the general population, provides a crucial vantage point for understanding how presumed genetic predisposition is manifested during developmental years...
July 2018: Journal of Child Psychology and Psychiatry, and Allied Disciplines
Sebastian Walther, Katharina Stegmayer
Diagnosis and treatment of motor phenomena in schizophrenia spectrum disorders Abstract. Motor abnormalities are intrinsic features of schizophrenia spectrum disorders. They may be spontaneous or antipsychotic drug-induced. The four most important symptom groups are abnormal involuntary movements or dyskinesia, Parkinsonism, catatonia and neurological soft signs. In addition, there are further motor abnormalities, which are less frequent and less operationalized. The suspected etiology of motor abnormalities is strongly associated with altered neurodevelopment...
June 2018: Therapeutische Umschau. Revue Thérapeutique
Franz Moggi
Epidemiology, etiology and treatment of patients with psychosis and co-morbid substance use disorder Abstract. More than 25 years ago, when the research on the efficacy of treatments for patients with a comorbidity of psychosis and substance use disorder has been systematically started, some authors described the treatment of these patients as a "mission impossible". Approximately half of all individuals with schizophrenia develop substance use disorders in the course of their life; about one third of them a comorbid alcohol use disorder and about one quarter a comorbid substance use disorder with other addictive substances...
June 2018: Therapeutische Umschau. Revue Thérapeutique
Eun-Jeong Kim, Yong-Ku Kim
Objective: Brain-derived neurotrophic factor (BDNF) has possible neurobiologic impact on etiology of schizophrenia. We hypothesized that the specific allele or the genotype such as two single nucleotide polymorphisms (SNPs) , 196G/A (rs6265), 11757G/C(rs16917204) is associated with schizophrenia or its clinical features. Methods: 241 normal controls and 157 schizophrenia patients are included. The differences in allele or genotype distribution for the patients and normal controls were analyzed...
July 2018: Psychiatry Investigation
Daqiang Sun, Christopher R K Ching, Amy Lin, Jennifer K Forsyth, Leila Kushan, Ariana Vajdi, Maria Jalbrzikowski, Laura Hansen, Julio E Villalon-Reina, Xiaoping Qu, Rachel K Jonas, Therese van Amelsvoort, Geor Bakker, Wendy R Kates, Kevin M Antshel, Wanda Fremont, Linda E Campbell, Kathryn L McCabe, Eileen Daly, Maria Gudbrandsen, Clodagh M Murphy, Declan Murphy, Michael Craig, Jacob Vorstman, Ania Fiksinski, Sanne Koops, Kosha Ruparel, David R Roalf, Raquel E Gur, J Eric Schmitt, Tony J Simon, Naomi J Goodrich-Hunsaker, Courtney A Durdle, Anne S Bassett, Eva W C Chow, Nancy J Butcher, Fidel Vila-Rodriguez, Joanne Doherty, Adam Cunningham, Marianne B M van den Bree, David E J Linden, Hayley Moss, Michael J Owen, Kieran C Murphy, Donna M McDonald-McGinn, Beverly Emanuel, Theo G M van Erp, Jessica A Turner, Paul M Thompson, Carrie E Bearden
The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date...
June 13, 2018: Molecular Psychiatry
Tian Zhang, Jun Li, Hao Yu, Yongyong Shi, Zhiqiang Li, Linyan Wang, Ziqi Wang, Tianlan Lu, Lifang Wang, Weihua Yue, Dai Zhang
Schizophrenia (SCZ) is a severe psychiatric disorder with evidence of a strong genetic component in the complex etiologies. Some studies indicated that gamma-aminobutyric acid (GABA)A receptor β2 subunit gene (GABRB2) was associated with SCZ. Other studies reported a negative association. Moreover, the results of two previous meta-analyses of GABRB2 with SCZ were inconsistent and the sample sizes were limited. Therefore, an updated meta-analysis combined with genome-wide association study (GWAS) data of the Han Chinese population and Psychiatric Genomics Consortium (PGC) was performed...
2018: PloS One
Yukio Ago, Atsuko Hayata, Hitoshi Hashimoto
The advent of the genomic era has led to the discovery of linkages of several genes and pathways to schizophrenia and autism spectrum disorder (ASD) that may serve as new biomarkers or therapeutic targets for these diseases. Two large-scale genetic studies published early in 2011 provided evidence that functional microduplications at 7q36.3, containing VIPR2, are a risk factor for schizophrenia. 7q36.3 microduplications were also reported to be significantly increased in ASD. VIPR2 encodes VPAC2, a seven transmembrane heterotrimeric G protein-coupled receptor that binds two homologous neuropeptides with high affinity, PACAP and VIP...
2018: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
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