Incidence Worldwide of Schizophrenia

Jablensky, Assen; Sartorius, Norman; Korten, A. E.; Ernberg, G.; Anker, Martha; Cooper, Jonathan; Day, Robert M.

doi:10.1192/s0007125000216802

Cited by 26 publications

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“…Schizophrenia (SCZ) and bipolar disorder (BPD) are two major psychiatric disorders which affect together approximately 3 % of the world's population and are recognized as leading causes of morbidity [1,2]. Family, twin, and adoption studies suggested a substantial genetic component together with environmental risk factors in the pathogenesis of these illnesses [3].…”

Section: Introductionmentioning

confidence: 99%

Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

Huang

Grigoroiu‐Serbanescu

et al. 2015

Mol Neurobiol

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Reelin (RELN) is identified as a risk gene for major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). However, the role of its downstream signaling molecule, the low-density lipoprotein receptor-related protein 8 (LRP8) in these illnesses is still unclear. To detect whether LRP8 is a susceptibility gene for SCZ and BPD, we analyzed the associations of single nucleotide polymorphisms (SNPs) in LRP8 in a total of 47,187 subjects (including 9379 SCZ patients; 6990 BPD patients; and 12,556 controls in a screening sample, and 1397 SCZ families, 3947 BPD patients, and 8387 controls in independent replications), and identified a non-synonymous SNP rs5174 in LRP8 significantly Ming Li and Liang Huang contributed equally to this work. Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-015-9559-6) contains supplementary material, which is available to authorized users. , odds ratio (OR)=1.066, 95 % confidence interval (CI)=1.035-1.098). The risk SNP rs5174 was also associated with LRP8 messenger RNA (mRNA) expression in multiple brain tissues across independent samples (lowest P=0.00005). Further exploratory analysis revealed that LRP8 was preferentially expressed in fetal brain tissues. Protein-protein interaction (PPI) analysis demonstrated that LRP8 significantly participated in a highly interconnected PPI network build by top risk genes for SCZ and BPD (P=7.0×10 −4). Collectively, we confirmed that LRP8 is a risk gene for psychosis, and our results provide useful information toward a better understanding of genetic mechanism involving LRP8 underlying risk of complex psychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

Huang

Grigoroiu‐Serbanescu

et al. 2015

Mol Neurobiol

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“…Incidence appears to be broadly stable over time and across cultures (Gottesman 1991;Jablensky et al 1992). It is substantially heritable (Gottesman 1991;Cardno et al 1999), though what is inherited is best described as a diathesis or vulnerability that may or may not lead to actual illness, and whose progression is affected by environmental factors .…”

Section: Introductionmentioning

confidence: 99%

Schizotypy, creativity and mating success in humans

2005

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There is an evolutionary puzzle surrounding the persistence of schizophrenia, since it is substantially heritable and associated with sharply reduced fitness. However, some of the personality traits which are predictive of schizophrenia are also associated with artistic creativity. Geoffrey Miller has proposed that artistic creativity functions to attract mates. Here, we investigate the relationship between schizotypal personality traits, creative activity, and mating success in a large sample of British poets, visual artists, and other adults. We show that two components of schizotypy are positively correlated with mating success. For one component, this relationship is mediated by creative activity. Results are discussed in terms of the evolution of human creativity and the genesis of schizophrenia.

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“…Subsequent treatment of the amidine starting material with the appropriate substituted chlorobutyrophenone afforded the target compound (I), 4-(4-(8-chloro-5H-dibenzo [b,e] [1,4] diazepin-11-yl) piperazin-1-yl)-1-p-tolylbutan-1-one, in respectable yield (24%) (Fig. 2).…”

Section: Synthesis Of the Target Compoundsmentioning

confidence: 99%

“…Schizophrenia is characterized by severely fragmented thought processes and a gross distortion of reality, and affects approximately 1% of the world's population [1].…”

Section: Introductionmentioning

confidence: 99%

“…Isosteric replacement is a tool commonly used by medicinal chemists whereby an atom(s) or functional groups of a chemical entity is replaced with groups of similar size with the aim of improving biological activity [28]. This pyridobenzoxazepine structural class has been previously investigated by Liégeois et al [29], with particular interest in the compound 8-chloro-5-(4-methylpiperazin-1-yl)-11H-pyrido[2,3-b] [1,5]benzoxazepine [also known as JL13 ( Fig. 1)], which is currently being clinically evaluated.…”

Section: Introductionmentioning

confidence: 99%

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New hybrids of clozapine and haloperidol and their isosteric analogues: synthesis, X-ray crystallography, conformational analysis and preliminary pharmacological evaluation

et al. 2010

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Schizophrenia is a debilitating mental disorder which affects approximately 1% of the world's population. Clozapine is an atypical antipsychotic showing unmatched effectiveness in the control of treatment-resistant schizophrenia. Unlike typical antipsychotics, clozapine does not induce extrapyramidal side effects (EPS), tardive dyskinesia or elevate prolactin levels. However, clozapine can induce a potentially fatal blood disorder, agranulocytosis, in 1-2% of patients, severely limiting its clinical use. The model for antipsychotic activity under investigation is based on obtaining a clozapine-like profile with preferential dopamine D 4 and serotonin 5-HT 2A receptor affinity. Profiled herein are three unique members of a series of prospective antipsychotic agents. Compound (I) originated from the structural hybridization of the commercial therapeutics, clozapine and haloperidol, whilst compounds (II) and (III) possess an alternative tricyclic nucleus derived from JL13; a clozapine-like atypical antipsychotic developed by Liégeois et al. These compounds have been synthesized and characterized by means of elemental analysis, IR, 1 H and 13 C-NMR spectroscopy, MS and X-ray diffraction. Compound (I) crystallizes in space group P(-1) with a = 10.5032 (1), b = 10.6261(2), c = 12.6214(3) Å , a = 81.432(1)°, b = 83.292(1)°, c = 61.604(1)°, Z = 2, V = 1223.62(4) Å 3 , C 28 H 29 ClN 4 O, M r = 473.00, D c = 1.284 Mg/m 3 , l = 0.185 mm -1 , F(000) = 500, R = 0.0506 and wR = 0.1304. Compound (II) crystallizes in the monoclinic space group P2 1 /c with a = 10.8212(2), b = 9.3592(2), c = 22.9494(5) Å , b = 106.471(1)°, Z = 4, V = 2228.88(8) Å 3 , C 25 H 25 ClN 4 O 2 , M r = 448.94, D c = 1.338 Mg/m 3 , l = 0.202 mm -1 , F(000) = 944, R = 0.0529 and wR = 0.1129. Compound (III) crystallizes in the monoclinic space group P2 1 /c with a = 10.5174(2), b = 9.3112(2), c = 24.2949(5) Å , b = 98.666(1)°, Z = 4, V = 2352.03(8) Å 3 , C 25 H 24 Cl 2 N 4 O 2 , M r = 483.38, D c = 1.365 Mg/m 3 , l = 0.306 mm -1 , F(000) = 1008, R = 0.0478 and wR = 0.1067. The solid state conformations of (I), (II) and (III) exhibit the characteristic V-shaped buckled nature of the respective dibenzodiazepine and pyridobenzoxazepine nuclei with the central seven-membered heterocycle in a boat conformation. The molecules of (I) form a head-to-tail dimeric motif stabilized by hydrogen bonding. The results of a conformational analysis of compounds (I)-(III) investigating the effect of environment (in vacuo and aqueous solution) are presented. These analogues were tested for in vitro affinity for the dopamine D 4 and serotonin 5-HT 2A receptors and their comparative receptor binding profiles to clozapine and JL13 are reported.

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Incidence Worldwide of Schizophrenia

Cited by 26 publications

References 0 publications

Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis

Schizotypy, creativity and mating success in humans

New hybrids of clozapine and haloperidol and their isosteric analogues: synthesis, X-ray crystallography, conformational analysis and preliminary pharmacological evaluation

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