Schizophrenia in identical twins

Narayan, Choudhary Laxmi; Shikha, Deep; Shekhar, Shivendra

doi:10.4103/0019-5545.166635

Cited by 9 publications

(4 citation statements)

References 4 publications

(4 reference statements)

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“…In addition to a genetic contribution, the environment also plays a key role in disease etiology [11]. This disorder is hereditary and the concordance of schizophrenia in monozygotic twins ranges from 41 to 79% [12][13][14]. Genome-wide association studies (GWAS) have been performed in schizophrenia with an approach to better understand the etiology of the disease.…”

Section: Introductionmentioning

confidence: 99%

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Stern,

Zhang,

Wang

et al. 2024

Mol Psychiatry

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Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Stern,

Zhang,

Wang

et al. 2024

Mol Psychiatry

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show abstract

“…In addition to a genetic contribution, the environment also plays a key role in disease etiology 11 . This disorder is hereditary and the concordance of schizophrenia in monozygotic twins ranges from 41%-79% [12][13][14] . Genome-wide association studies (GWAS) have been performed in SCZ with an approach to better understand the etiology of the disease.…”

Section: Introductionmentioning

confidence: 99%

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Stern

Zhang

Wang

et al. 2022

Preprint

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Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. We characterized human-induced pluripotent stem cell (iPSC)-derived hippocampal neurons from two pairs of monozygotic twins that are discordant for a schizophrenia diagnosis. We compared the affected and the non-affected siblings and compared all of them to twin sets where none of the siblings suffered from schizophrenia. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. The neurons in the unaffected co-twin group were also less arborized than the neurons from controls but more arborized than those from affected siblings. Some of their spike features were immature (but less immature than neurons derived from the affected siblings). Importantly, their synaptic activity was not affected. Since schizophrenia is a genetically complex disorder, our twin study allows the measurement of neuronal phenotypes with a similar genetic background. The differences between the siblings may arise due to changes that occurred after the split of the egg into twins. Therefore, our study confirms that dysregulation of synaptic pathways, as well as changes in the rate of synaptic events, distinguishes between individuals affected with schizophrenia and unaffected individuals, even in those having a very similar genetic background.

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“…Considerable examinations have indicated that if a close family member has SCZ, other family members are at a much increased risk [4]. Furthermore, multiple investigations into identical twins reveal that genetic factors account for 50% of the possibility of having the disorder [5]. This implies that environmental forces, including epigenetic transformations in the DNA, are to blame for the remaining 50% of the disease.…”

Section: Introductionmentioning

confidence: 99%

The correlation between promoter methylation status and expression of KLF9 and MYH11 in Schizophrenia

Davarinejad

Foruzandeh

Golmohammadi

et al. 2022

Preprint

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In the current study, Methylation and expression microarray data related to Schizophrenia (SCZ) were analyzed to identify genes whose aberrant promoter methylation could play a crucial role in the dysregulation of gene expression. After data analysis, two genes including KLF9 and MYH11 were identified. Considering CpG sites in the promoter region of the mentioned genes using Methprimer database, Bisulfite specific primer (BSP) was designed, and Methylation specific-high resolution melting (MS-HRM) analysis was performed to assess the promoter methylation status of the genes, and also real-time PCR was used to evaluate mRNA expression level of KLF9 and MYH11 in 50 SCZ and healthy control specimens. The results show 62% hypermethylation and 38% hypomethylation of KLF9 in SCZ samples and 34% hypermethylation and 66% hypomethylation in healthy control samples. MYH11 promoter shows 54% hypermethylation and 46% hypomethylation in SCZ samples while 28% hypermethylation and 72% hypomethylation in healthy controls. The result of real-time PCR shows downregulation of KLF9 and MYH11 in SCZ samples compared with healthy samples. The aberrant methylation has a direct effect on the expression of mentioned genes.

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Schizophrenia in identical twins

Cited by 9 publications

References 4 publications

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission

The correlation between promoter methylation status and expression of KLF9 and MYH11 in Schizophrenia

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