<i>DISC1</i> gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

Shokouhifar, Alireza; Askari, Nahid; Yazdani, Shaghayegh; Mehrabadi, Jalil Fallah

doi:10.1002/jcb.27427

Cited by 7 publications

(3 citation statements)

References 21 publications

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“…W skali świata rozpowszechnienie schizofrenii szacuje się na około 0,80% populacji w wieku powyżej 18. roku życia, co oznacza, że aktualnie żyje około 10 milionów ludzi z różnymi formami psychoz (Shokouhifar et al, 2018;Yang et al, 2016). W świetle przewidywanego wzrostu długości życia liczba ta podwoi się do roku 2030, a potroi -do 2050 (Toulopoulou et al, 2017).…”

Section: Wprowadzenieunclassified

Selected risk factors for schizophrenia: between the diversity of aetiological models and personalised psychiatry

Śmierciak

Krzyściak

Szwajca

et al. 2018

PSYCHIATR. PSYCHOL. KLIN.

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Schizofrenia należy do coraz poważniejszych problemów medycznych i społecznych. Pomimo postępu w farmakoterapii i innych formach terapii psychoz pozostaje ona zaburzeniem o chronicznym i degradującym przebiegu. Kilka dekad badań nad jej uwarunkowaniami nie przyniosło odkrycia etiologii choroby. Potwierdzone w badaniach i zweryfikowane w praktyce klinicznej hipotezy nie tłumaczą przyczyn jej powstawania lub ograniczają się do wyjaśnienia tylko części manifestowanych objawów. Przykładem mogą być szeroko znane i opisane modele zaburzenia neurotransmisji dopaminergicznej (teoria dopaminowa) czy serotoninergicznej, na których opiera się współczesna farmakoterapia. Jest to jednak interwencja nie ingerująca w mechanizmy powstawania choroby, lecz tylko usuwająca część objawów, bez wpływu na deficyty poznawcze. Coraz częściej w badaniach nad czynnikami ryzyka schizofrenii -w tym zwłaszcza jej pierwszego epizodu -podnosi się znaczenie interakcji między dysregulacją immunologiczną, zaburzeniami równowagi oksydacyjno-antyoksydacyjnej, zakłóceniami bariery jelitowej oraz zjawiskami o charakterze epigenetycznym. Fakt ten wskazuje na konieczność zmodyfikowania klasycznych metakoncepcji nt. rozwoju schizofrenii o wymiar oddziaływania pomiędzy szeregiem różnorodnych zjawisk biologicznych a zjawiskami psychospołecznymi. W literaturze przedmiotu znaleźć można wiele pojedynczych obserwacji, brakuje jednak przekrojowych badań, w których sprawdzano by zależności między zjawiskami immunologicznymi i zapalnymi, ekspresją genów a dynamiką zmian stanu klinicznego w przebiegu leczenia. Przedstawione w tekście mechanizmy etiopatogenezy choroby stanowią potencjalny cel przyszłych strategii badawczych, które dodatkowo powinny wzmacniać podejście spersonalizowane i potencjał terapii skojarzonych.Słowa kluczowe: schizofrenia, modele etiologiczne, czynniki zapalno-immunologiczne, stres oksydacyjny, bariera jelitowa Schizophrenia is a very serious and growing medical and social problem. Despite advances in pharmacotherapy and other forms of psychosis therapy, schizophrenia remains a chronic and degrading disorder. Several decades of research on the determinants of schizophrenia brought no insight into its aetiology. Hypotheses confirmed in the studies and verified in clinical practice either fail to account for the causes of schizophrenia or explain only some of its manifestations. The well-known and widely described models of impaired dopaminergic (the dopamine hypothesis) or serotonergic neurotransmission, which provide foundations for the contemporary pharmacotherapy, may serve as an example. However, such an intervention does not interfere with the mechanisms underlying the disease, but only eliminates some of the symptoms, with no effects on cognitive deficits. Studies on risk factors for schizophrenia, its first episode in particular, increasingly emphasise the importance of interactions between immunological dysregulation, oxidant-antioxidant imbalance, disturbances of the intestinal barrier and epigenetic phenomena. This fact points to th...

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Section: Wprowadzenieunclassified

Selected risk factors for schizophrenia: between the diversity of aetiological models and personalised psychiatry

Śmierciak

Krzyściak

Szwajca

et al. 2018

PSYCHIATR. PSYCHOL. KLIN.

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“…The disrupted‐in‐schizophrenia 1 (DISC1) gene was initially identified in a Scottish family with an unusually high prevalence of mental disorders, including schizophrenia, and the disruption was due to a balanced translocation of the chromosome (1:11) (q43, q21) (Millar et al., 2001). The DISC1 protein signaling pathway has been linked to multiple deficits in brain development both in humans and animals, which may lead to schizophrenia, bipolar disorder, recurrent major depression, and other neuropsychiatric disorders in humans, as well as phenotypical alterations reminiscent of human psychiatric disorders in animals (Austin et al., 2003; Clapcote et al., 2007; Hashimoto et al., 2006; Kirsty Millar et al., 2000; Shokouhifar et al., 2019). Recently, several studies have shown that the neural dysregulation caused by DISC1 impairs the Dopamine (DA) system by increasing the affinity of DA‐D2 receptors and increasing the removal of DA from the synaptic cleft because of translocation of the DA transporter, resulting in decreasing DA levels in the dorsal striatum, amygdala, and hippocampus (HPC, Hennah & Porteous, 2009; Ripke et al., 2014; Trossbach et al., 2016; Wang et al., 2017).…”

Section: Introductionmentioning

confidence: 99%

50‐kHz ultrasonic vocalizations do not signal social anhedonia in transgenic DISC1 rats

et al. 2023

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Patients diagnosed with neuropsychiatric disorders, such as autism and schizophrenia, suffer from disorganized speech. The disrupted-in-schizophrenia 1 (DISC1) protein pathway is considered a risk factor for the development of several psychiatric disorders and plays an important role in the dysregulation of dopamine (DA), which in turn plays an important role in the regulation of ultrasonic vocalizations (USVs) in rats. Moreover, the DISC1 protein pathway has been identified as a cause of social anhedonia, that is, a decrease in the drive for social interactions. USVs transmit specific affective information to other rats, with 50-kHz calls indicating a positive affective state in rats. Dysregulation of the dopaminergic system impacts the qualitative and quantitative features of USVs, such as duration, peak frequency, and the call rate. In this study, we thus used a well-established transgenic DISC1 (tgDISC1) rat line to investigate whether the neural (decreased DA levels in the dorsal striatum, amygdala, and hippocampus (HPC)) and behavioral (social anhedonia) features of tgDISC1 rats could be manifested through the modulation of their 50-kHz USVs. Analyses of three features (call rate, duration, and peak frequency) of all 50-kHz revealed no significant differences between groups, suggesting decreased DA levels in the dorsal striatum and amygdala, and HPC may affect social interaction but leave 50-kHz USV production intact.

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“…DISC1 was originally identified in a Scottish family where chromosomal translocation directly disrupted brain-expressed genes associated with several psychological disorders, such as schizophrenia, bipolar disorder, and recurrent major depression (Millar et al, 2000; Blackwood et al, 2001). Alterations in the DISC1 gene are associated with impairments in brain development in humans, as well as primates and rodents, explicating a possible mechanism for their role in several psychiatric disorders (Austin et al, 2003; Hashimoto et al, 2006; Clapcote et al, 2007; Shokouhifar et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Reduced motivation for social contact in Disrupted-in-schizophrenia transgenic rats

Seidisarouei¹,

M²,

Schäble³

et al. 2021

Preprint

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The Disrupted-in-schizophrenia 1 (DISC1) signaling pathway is considered to play a key role in schizophrenia, depression, autism and other psychiatric disorders. DISC1 is involved in regulating the dopaminergic neurotransmission in, among others, the mesolimbic reward system. A transgenic rat line tgDISC1 has been introduced as a model system to study behavioral phenotypes associated with abnormal DISC1 pathways. Here, we evaluated the impact of impaired DISC1 signaling on social (social interaction) and non-social (sucrose) reward preferences in the tgDISC1 animal model. In a plus-maze setting, rats chose between the opportunity for social interaction with an unfamiliar juvenile conspecific (social reward) or drinking sweet solutions with variable sucrose concentrations (non-social reward). tgDISC1 rats differed from wild-type rats in their social, but not in their non-social reward preferences. Specifically, DISC1 rats showed a lower interest in interaction with the juvenile conspecific, but did not differ from wild-type rats in their preference for higher sucrose concentrations. These results suggest that disruptions of the DISC1 pathway that is associated with altered dopamine transmission in the brain result in selective deficits in social motivation seen in neuropsychiatric illness.

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DISC1 gene polymorphisms and the risk of schizophrenia in an Iranian population: A preliminary study

Cited by 7 publications

References 21 publications

Selected risk factors for schizophrenia: between the diversity of aetiological models and personalised psychiatry

Selected risk factors for schizophrenia: between the diversity of aetiological models and personalised psychiatry

50‐kHz ultrasonic vocalizations do not signal social anhedonia in transgenic DISC1 rats

Reduced motivation for social contact in Disrupted-in-schizophrenia transgenic rats

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