Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

doi:10.1186/s13073-018-0518-5

. 2018 Jan 31;10(1):9.

doi: 10.1186/s13073-018-0518-5.

Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

Xinyuan Wang^{1

2}, Kimberly M Christian¹, Hongjun Song^{1

3

4

5}, Guo-Li Ming^{6

7

8

9}

Affiliations

¹ Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
² School of Basic Medical Sciences, Fudan University, Shanghai, 200040, China.
³ Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴ Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁵ The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁶ Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.
⁷ Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.
⁸ Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.
⁹ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.

PMID: 29386063
PMCID: PMC5793422
DOI: 10.1186/s13073-018-0518-5

Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

Xinyuan Wang et al. Genome Med. 2018.

. 2018 Jan 31;10(1):9.

doi: 10.1186/s13073-018-0518-5.

Authors

Xinyuan Wang^{1

2}, Kimberly M Christian¹, Hongjun Song^{1

3

4

5}, Guo-Li Ming^{6

7

8

9}

Affiliations

¹ Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
² School of Basic Medical Sciences, Fudan University, Shanghai, 200040, China.
³ Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁴ Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁵ The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
⁶ Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.
⁷ Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.
⁸ Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.
⁹ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA. gming@pennmedicine.upenn.edu.

PMID: 29386063
PMCID: PMC5793422
DOI: 10.1186/s13073-018-0518-5

Abstract

Breakthroughs on many fronts have provided strong evidence to support synaptic dysfunction as a causal factor for neuropsychiatric diseases. Genetic studies have identified variants implicated in novel biological and synaptic pathways, and animal and patient-derived induced pluripotent stem cell-based models have allowed mechanistic investigations of synaptic dysfunction in pathological processes.

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Conflict of interest statement

Competing interests

The authors declare that they have no competing interests.

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Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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References

1. Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–427. doi: 10.1038/nature13595. - DOI - PMC - PubMed
1. Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177–183. doi: 10.1038/nature16549. - DOI - PMC - PubMed
1. Petanjek Z, Judaš M, Šimić G, Rašin MR, Uylings HBM, Rakic P, et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. PNAS. 2011;108:13281–13286. doi: 10.1073/pnas.1105108108. - DOI - PMC - PubMed
1. Ishizuka K, Fujita Y, Kawabata T, Kimura H, Iwayama Y, Inada T, et al. Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders. Transl Psychiatry. 2017;7:e1184. doi: 10.1038/tp.2017.173. - DOI - PMC - PubMed
1. Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011;473:221–225. doi: 10.1038/nature09915. - DOI - PMC - PubMed

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[1] Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–427. doi: 10.1038/nature13595. - DOI - PMC - PubMed

[2] Schizophrenia Working Group of the Psychiatric Genomics Consortium Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511:421–427. doi: 10.1038/nature13595. - DOI - PMC - PubMed

[3] Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177–183. doi: 10.1038/nature16549. - DOI - PMC - PubMed

[4] Sekar A, Bialas AR, de Rivera H, Davis A, Hammond TR, Kamitaki N, et al. Schizophrenia risk from complex variation of complement component 4. Nature. 2016;530:177–183. doi: 10.1038/nature16549. - DOI - PMC - PubMed

[5] Petanjek Z, Judaš M, Šimić G, Rašin MR, Uylings HBM, Rakic P, et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. PNAS. 2011;108:13281–13286. doi: 10.1073/pnas.1105108108. - DOI - PMC - PubMed

[6] Petanjek Z, Judaš M, Šimić G, Rašin MR, Uylings HBM, Rakic P, et al. Extraordinary neoteny of synaptic spines in the human prefrontal cortex. PNAS. 2011;108:13281–13286. doi: 10.1073/pnas.1105108108. - DOI - PMC - PubMed

[7] Ishizuka K, Fujita Y, Kawabata T, Kimura H, Iwayama Y, Inada T, et al. Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders. Transl Psychiatry. 2017;7:e1184. doi: 10.1038/tp.2017.173. - DOI - PMC - PubMed

[8] Ishizuka K, Fujita Y, Kawabata T, Kimura H, Iwayama Y, Inada T, et al. Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders. Transl Psychiatry. 2017;7:e1184. doi: 10.1038/tp.2017.173. - DOI - PMC - PubMed

[9] Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011;473:221–225. doi: 10.1038/nature09915. - DOI - PMC - PubMed

[10] Brennand KJ, Simone A, Jou J, Gelboin-Burkhart C, Tran N, Sangar S, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011;473:221–225. doi: 10.1038/nature09915. - DOI - PMC - PubMed

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Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

Affiliations

Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

Authors

Affiliations

Abstract

Conflict of interest statement

Competing interests

Publisher’s Note

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Cited by

References

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Medical

Abstract

Conflict of interest statement

Competing interests

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