A Human Open Field Test Reveals Thigmotaxis Related to Agoraphobic Fear

Walz, Nora; Mühlberger, Andreas; Pauli, Paul

doi:10.1016/j.biopsych.2015.12.016

Cited by 105 publications

(80 citation statements)

References 25 publications

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“…Consistent with our findings in humans and extending the known phenotype of the spastic mouse, we showed that partial Glrb knock-out mice exhibited avoidance of a novel open space, a behavior we recently confirmed to be related to agoraphobic fear in humans 3 . At the mechanistic level, it is somewhat puzzling that the phenotype-associated rs7688285 A allele in fact was not found with decreased, but instead increased GLRB expression in a heterologous cell system as well as in post mortem samples.…”

Section: Discussionsupporting

confidence: 91%

“…AG is a clinical condition characterized by abnormal open space behavior 3 and, importantly, distorted cognitive processes 4 thus reflecting a dimensional phenotype which can be assessed with the Agoraphobic Cognitions Questionnaire (ACQ) 5 . Family studies reveal familial aggregation in PD and AG 6,7 and twin studies estimated heritabilities of about 38% and 48%, with a genetic correlation of 0.83 between both disorders 8 .…”

Section: Introductionmentioning

confidence: 99%

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GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder

et al. 2017

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The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG -related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1,370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, p=3.3x10 -8 ; rs191260602, p=3.9x10 -8 ). We followed up on this finding in a larger dimensional ACQ sample (N=2,547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3,845) and a casecontrol sample with the categorical phenotype PD/AG (N combined =1,012) obtaining highly Partial Glrb knockout-mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, though functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder

et al. 2017

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“…This behavior has been identified in teleosts(Ahmad and Richardson, 2013), rodents(Simon et al, 1994), and in humans (Walz et al, 2015). It is thought that thigmotaxis is a way of finding shelter, protection or a way of escape from a predator or stressor (Sharma et al, 2009).…”

Section: Methodsmentioning

confidence: 98%

Behavioral, morphometric, and gene expression effects in adult zebrafish (Danio rerio) embryonically exposed to PFOA, PFOS, and PFNA

2016

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Perfluoroalkylated substances (PFAS) are a class of persistent anthropogenic chemicals that have been detected worldwide. PFASs consist of fluorinated carbon chains of varying length, terminal groups, and have a number of industrial uses. A previous zebrafish study from our laboratory showed that acute (3–120 h post fertilization, 0.02–2.0μM), waterborne embryonic exposure to these chemicals resulted in chemical specific alterations at 5 days post fertilization (dpf), and some effects persisted up to 14 dpf. Using a gene battery consisting of 100 transcripts identified several genes that were up or down regulated. This current study looks at the long-term impacts of PFASs in adult zebrafish using the same exposure regimen. It was hypothesized that sub-lethal exposure of perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), or perfluorooctane sulfonate (PFOA) in embryonic zebrafish (3–120 hpf) would result in permanent morphometric, gene expression, and behavioral changes in adult fish similar to those observed at 5 and 14 dpf. Zebrafish were exposed to PFOS, PFOA, and PFNA (Control 0μM, 2.0μM) for the first five days post fertilization. At six months post fertilization, no PFAS treatment resulted in a significant change in total body length or weight. In terms of behavior, PFNA males showed a reduction in total distance traveled and time of immobility, and an increase in thigmotaxis behavior, aggressive attacks, and preference for the bright section of the tank. PFOS treated males had a reduced aggression behavior, and PFOA females preferred the dark section of the tank. Gene expression of slco2b1, slco1d1, and tgfb1a were analyzed because these transcripts were previously found to be affected by PFAS exposure in 5dpf and 14 dpf zebrafish and resulted in: significant decrease in expression of slco2b1 for both sexes in PFNA and PFOS treated groups, significant decrease of slco1d1 in all treatment groups for females and PFOS and PFOA exposed males, significant increase of tgfb1a in males treated with PFOS and PFNA, and a significant increase of bdnf in all PFAS male groups. This study demonstrates that acute, embryonic exposure (5 days) to individual PFASs result in significant biochemical and behavioral changes in young adult zebrafish 6 months after exposure. These three PFASs have long term and persistent impacts following short term embryonic exposure that persists into adulthood.

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“…In this issue of Biological Psychiatry , Walz et al . (1) present results of a human analog paradigm to the rodent open field test (OFT) (2) to quantitatively measure the proclivity for avoidance of open spaces, the core symptom of agoraphobia.…”

mentioning

confidence: 99%