Department of Economics and Business Economics

Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions. / Giovanoli, Sandra; Werge, Thomas M; Mortensen, Preben B; Didriksen, Michael; Meyer, Urs.

In: Neuropsychopharmacology, Vol. 44, No. 4, 2019, p. 703–710.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Giovanoli, S, Werge, TM, Mortensen, PB, Didriksen, M & Meyer, U 2019, 'Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions', Neuropsychopharmacology, vol. 44, no. 4, pp. 703–710. https://doi.org/10.1038/s41386-018-0189-3

APA

CBE

MLA

Vancouver

Author

Giovanoli, Sandra ; Werge, Thomas M ; Mortensen, Preben B ; Didriksen, Michael ; Meyer, Urs. / Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions. In: Neuropsychopharmacology. 2019 ; Vol. 44, No. 4. pp. 703–710.

Bibtex

@article{21221c4132294943a3fe19b48ae328a4,
title = "Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions",
abstract = "15q13.3 microdeletion is one of several gene copy number variants (CNVs) conferring increased risk of psychiatric and neurological disorders. This microdeletion gives rise to a variable spectrum of pathological phenotypes, ranging from asymptomatic to severe clinical outcomes. The reasons for these varying phenotypic outcomes remain unknown. Using a mouse model of hemizygous deletion of the orthologous region of 15q13.3, the present study examined whether exposure to stressful life events might interact with hemizygous 15q13.3 microdeletion in the development of behavioral dysfunctions. We show that hemizygous 15q13.3 microdeletion alone induces only limited effects on adult behaviors, but when combined with psychological stress in pubescence (postnatal days 30-40), it impairs sensorimotor gating and increases the sensitivity to the psychostimulant drug, amphetamine, at adult age. Stress exposure in adolescence (postnatal days 50-60) did not induce similar interactions with 15q13.3 microdeletion, but led to impaired emotional learning and memory and social behavior regardless of the genetic background. The present study provides the first evidence for interactive effects between hemizygous 15q13.3 microdeletion and exposure to stressful life events, and at the same time, it emphasizes an important influence of the precise timing of postnatal stress exposure in these interactions. Our findings suggest that hemizygous 15q13.3 microdeletion can act as a {"}disease primer{"} that increases the carrier's vulnerability to the detrimental effects of peripubertal stress exposure on adult behaviors.",
keywords = "ANIMAL-MODELS, AUTISM, ENDOPHENOTYPE, EXTINCTION, FEAR, IMMUNE ACTIVATION, MENTAL-RETARDATION, MOUSE MODEL, PREPULSE INHIBITION, SCHIZOPHRENIA",
author = "Sandra Giovanoli and Werge, {Thomas M} and Mortensen, {Preben B} and Michael Didriksen and Urs Meyer",
year = "2019",
doi = "10.1038/s41386-018-0189-3",
language = "English",
volume = "44",
pages = "703–710",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "4",

}

RIS

TY - JOUR

T1 - Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions

AU - Giovanoli, Sandra

AU - Werge, Thomas M

AU - Mortensen, Preben B

AU - Didriksen, Michael

AU - Meyer, Urs

PY - 2019

Y1 - 2019

N2 - 15q13.3 microdeletion is one of several gene copy number variants (CNVs) conferring increased risk of psychiatric and neurological disorders. This microdeletion gives rise to a variable spectrum of pathological phenotypes, ranging from asymptomatic to severe clinical outcomes. The reasons for these varying phenotypic outcomes remain unknown. Using a mouse model of hemizygous deletion of the orthologous region of 15q13.3, the present study examined whether exposure to stressful life events might interact with hemizygous 15q13.3 microdeletion in the development of behavioral dysfunctions. We show that hemizygous 15q13.3 microdeletion alone induces only limited effects on adult behaviors, but when combined with psychological stress in pubescence (postnatal days 30-40), it impairs sensorimotor gating and increases the sensitivity to the psychostimulant drug, amphetamine, at adult age. Stress exposure in adolescence (postnatal days 50-60) did not induce similar interactions with 15q13.3 microdeletion, but led to impaired emotional learning and memory and social behavior regardless of the genetic background. The present study provides the first evidence for interactive effects between hemizygous 15q13.3 microdeletion and exposure to stressful life events, and at the same time, it emphasizes an important influence of the precise timing of postnatal stress exposure in these interactions. Our findings suggest that hemizygous 15q13.3 microdeletion can act as a "disease primer" that increases the carrier's vulnerability to the detrimental effects of peripubertal stress exposure on adult behaviors.

AB - 15q13.3 microdeletion is one of several gene copy number variants (CNVs) conferring increased risk of psychiatric and neurological disorders. This microdeletion gives rise to a variable spectrum of pathological phenotypes, ranging from asymptomatic to severe clinical outcomes. The reasons for these varying phenotypic outcomes remain unknown. Using a mouse model of hemizygous deletion of the orthologous region of 15q13.3, the present study examined whether exposure to stressful life events might interact with hemizygous 15q13.3 microdeletion in the development of behavioral dysfunctions. We show that hemizygous 15q13.3 microdeletion alone induces only limited effects on adult behaviors, but when combined with psychological stress in pubescence (postnatal days 30-40), it impairs sensorimotor gating and increases the sensitivity to the psychostimulant drug, amphetamine, at adult age. Stress exposure in adolescence (postnatal days 50-60) did not induce similar interactions with 15q13.3 microdeletion, but led to impaired emotional learning and memory and social behavior regardless of the genetic background. The present study provides the first evidence for interactive effects between hemizygous 15q13.3 microdeletion and exposure to stressful life events, and at the same time, it emphasizes an important influence of the precise timing of postnatal stress exposure in these interactions. Our findings suggest that hemizygous 15q13.3 microdeletion can act as a "disease primer" that increases the carrier's vulnerability to the detrimental effects of peripubertal stress exposure on adult behaviors.

KW - ANIMAL-MODELS

KW - AUTISM

KW - ENDOPHENOTYPE

KW - EXTINCTION

KW - FEAR

KW - IMMUNE ACTIVATION

KW - MENTAL-RETARDATION

KW - MOUSE MODEL

KW - PREPULSE INHIBITION

KW - SCHIZOPHRENIA

UR - http://www.scopus.com/inward/record.url?scp=85053052752&partnerID=8YFLogxK

U2 - 10.1038/s41386-018-0189-3

DO - 10.1038/s41386-018-0189-3

M3 - Journal article

C2 - 30188511

VL - 44

SP - 703

EP - 710

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 4

ER -