Schizophrenia

Owen, Michael John; Sawa, Akira; Mortensen, Preben Bo

doi:10.1016/s0140-6736(15)01121-6

Cited by 1,421 publications

(1,246 citation statements)

References 141 publications

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“…Schizophrenia is a complex syndromic disease 29 with geographically varying prevalence 30 and characterized by a markedly elevated prevalence among first and second generation immigrants 31,32 , particularly among persons with dark skin moving to Nordic lattitudes 33 . These not peer-reviewed) is the author/funder.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

Hagen

Gonçalves

Hedley

et al. 2017

Preprint

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Mitochondria play a significant role in human diseases. However, disease associations with mitochondrial DNA (mtDNA) SNPs have proven difficult to replicate. A reanalysis of eight schizophrenia-associated mtDNA SNPs, in 23,743 normal Danes and 2,538 schizophrenia patients, revealed marked inter-allelic differences in haplogroup affiliation and nuclear ancestry, genogeophraphic affinity (GGA). This bi-genomic linkage disequilibrium (2GLD) could entail population stratification. Only two mitochondrial SNPs, m.15043A and m.15218G, were significantly associated with schizophrenia. However, these associations disappeared when corrected for haplogroup affiliation. The extensive 2GLD documented is a major concern when interpreting historic as well as designing future mtDNA association studies.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/149070 doi: bioRxiv preprint first posted online 3 Genetic variants in mitochondrial DNA (mtDNA) -and in nuclear genes coding for mitochondrial function -have been associated with disease 1-3 . More than 300 variants 4,5 in mtDNA and genes involved in mitochondrial function 6 have been reported to cause mitochondrial disease which is clinically characterised by complex metabolic, neurological, muscular and psychiatric symptoms 7,8 .SNPs in mtDNA and mitochondrial haplogroups (mtDNA hgs), which are evolutionarily fixed SNP sets with a characteristic geographical distribution, have been proposed as potential disease modifiers 8 . This has been reported in neurological degenerative diseases such as Alzheimer's disease 9-12 and Parkinson's disease 12-14 , metabolic diseases and cancers 15 , as well as psychiatric diseases, notably schizophrenia (SZ) and bipolar disease [16][17][18] .Association studies of mtDNA variants and disease have been difficult to replicate 8 . However, the definition of a methodological paradigm for association studies with mtDNA variants 19 implicitly assumes that mtDNA variants are independent of the nuclear genome. In a recent Danish study on mtDNA haplogroups and their nuclear ancestry or nuclear genogeographical affinity (GGA), we demonstrated a marked difference in nuclear ancestry between individual haplogroups 20 . This means that mtDNA hgs entail population stratification also at the level of gDNA. The effect of such a stratification on disease association, will depend on the admixture structure of the particular population, the population history, epidemiology and genetic epidemiology of the disease, as well as the number of persons included in the study. The extensive fine-scale heterogeneity of gDNA and significant admixture documented in the UK 21 and Europe 22 further increase the risk of spurious false positive associations, if the mtDNA/gDNA interaction is not corrected phenomenon for in association studies.not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The co...

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

Hagen

Gonçalves

Hedley

et al. 2017

Preprint

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“…1 Schizophrenia affects 21 million people worldwide and its prevalence in India is 4.3 to 8.7 million.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotics in schizophrenia: a retrospective study of drug utilization pattern in outpatient department of psychiatry at a tertiary care hospital

Patted

Hema

Nagaraj

2017

Int J Basic Clin Pharmacol

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Background: Psychiatric disorders are one of the major causes of morbidity and the burden of illness is enormous and remains grossly under represented. Psychotropic drugs have had a remarkable impact in psychiatric practice. Currently a large number of atypical antipsychotics available in the market are endorsed as better options for treating schizophrenia than the typical antipsychotics. The main objective of the study was to find the commonly prescribed antipsychotics in schizophrenia patients in a tertiary care center.Methods: After Institutional Ethics Committee approval, a retrospective cross-sectional drug utilization study of 400 prescriptions was under taken from 1st July 2015 to 30th July 2016 in the outpatient department of psychiatry of a tertiary care hospital. The prescribing pattern of antipsychotics in schizophrenia patients (N=107) was measured.Results: Out of 400 cases in the outpatient department, schizophrenia cases were predominant (N=107 i.e. 27%) out of which 42.1% were females and 57.9% were males. This was followed by mood disorders and neurotic & somatoform disorders. The most common antipsychotic used was olanzapine followed by risperidone. Least commonly used antipsychotic was haloperidol. Most of the patients who received risperidone also received an anticholinergic trihexyphenidyl (91.8%).Conclusions: Olanzapine and risperidone are the most commonly used antipsychotics. Anticholinergics should be used only in selected patients on antipsychotics as tolerance develops to extrapyramidal side effects. Anticholinergics are unnecessary after 3-6 months in all except 10% of patients. Moreover, it has its own side effects and adversely interacts with antipsychotics.

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“…Many of these variations are neither necessary nor sufficient to determine the disease and require an additional interaction with environmental factors to produce the manifestations that we call symptoms [2]. This is what we can observe, even in disorders with heritabilities over 70-80%, such as bipolar disorder [3] or schizophrenia [4,5]. Thus, the post-genomic era brought with it a greater blurring of the boundaries between normality and disease.…”

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confidence: 97%

Neurobiology of mental illness: from reductionism to integration

Macedo¹

2017

IJCNMH

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From its inception until now, psychiatry has continually searched for knowledge of brain-behavior relationships and the neurobiological underpinnings of psychopathology. The tendency to view mental illnesses as brain diseases is not new and goes back to Hippocrates, being dominant in the nineteenth century. This theoretical tradition was interrupted during the first decades of the twentieth century by a predominant psychological vision, embodied in different theories such as psychoanalysis, and a range of behavioural, humanistic and cognitive perspectives. However, in the last forty years the tendency to view psychiatric patients as individuals who have some kind of brain disorder has grown to the point of being an almost indisputable truth. In the second edition of Biological Psychiatry, Michael Trimble [1] said that biological psychiatry has a long past-which establishes its respectability-but a short history-which establishes its scientificity. Indeed, this part of the story is relatively short and researchers all over the world continue to struggle for discovering the

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Schizophrenia

Cited by 1,421 publications

References 141 publications

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

Mitochondrial DNA SNPs associated with Schizophrenia exhibit Highly Variable Inter-allelic Haplogroup Affiliation and Nuclear Genogeographic Affinity: Bi-Genomic Linkage Disequilibrium raises Major Concerns for Link to Disease

Antipsychotics in schizophrenia: a retrospective study of drug utilization pattern in outpatient department of psychiatry at a tertiary care hospital

Neurobiology of mental illness: from reductionism to integration

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